bims-fibdiv Biomed News
on Fibroblast diversity
Issue of 2026–03–01
fifty papers selected by
Emilio Ernesto Méndez Olivos, University of Calgary
  1. Structural maintenance of chromosome protein 1A exacerbates liver fibrosis by enhancing hepatic stellate cell activation and extracellular matrix synthesis via laminin subunit gamma 2 activation.
  2. Deficiency of NF-Erythroid 2-Related Factor 2 Exacerbates the Scar Through ERK Signaling Pathway.
  3. WISP1 drives a mechanically active immune modulatory and proliferative cardiac myofibroblast state.
  4. Adipose Tissue Extracellular Matrix Remodeling: A Driver of Obesity and Insulin Resistance.
  5. Serpine1 Regulates the Enhanced Inhibitory Effect of CHIR99021 Combined with Fibroblast Growth Factor 2 on Myocardial Fibrosis After Myocardial Infarction in Mice.
  6. ECM remodeling-associated immune signatures and hub proteins: predictive markers and therapeutic targets for metastatic gastric cancer.
  7. PHLDA1 is a shared diagnostic and key mediator of inflammatory fibrosis in heart and kidney.
  8. Interleukin-4 changes the transcriptome, ECM-associated components and function of mare endometrial fibroblast: Insights from healthy and fibrotic cells.
  9. Prolyl 3-Hydroxylase 2 Supports a Pro-Angiogenic Milieu Promoting Colorectal Cancer Progression and Metastasis.
  10. Ferrochel Alleviates Renal Fibrosis by Modulating Fibrogenesis and Epithelial-to-Mesenchymal Transition: In Vitro and In Vivo Studies.
  11. Microbiota-fibroblast crosstalk represents the missing link in skin barrier dysfunction and fibrosis.
  12. The Fibro-Immune Landscape Across Organs: A Single-Cell Comparative Study of Human Fibrotic Diseases.
  13. Unravelling the pathogenesis and therapeutic approaches of pancreatic ductal adenocarcinoma.
  14. LXN-THBS2 Signaling Axis Regulates Hepatic Stellate Cell Activation and Promotes the Development of Liver Fibrosis.
  15. Adventitial Fibrosis and Fibroblast Mechanosensitivity Are Shaped by Sex and Hormonal Status in Pulmonary Arterial Hypertension.
  16. The Tet3 degrader Bobcat339 ameliorates isoprenaline induced cardiac fibrosis and heart failure: animal and transcriptomic studies.
  17. N-Cadherin Dynamically Regulates Schwannoma Migration and Represents a Novel Therapeutic Target in NF2-Related Schwannomatosis.
  18. CACNB2 overexpression suppresses atrial fibroblast activation and atrial fibrosis to mitigate atrial fibrillation.
  19. Structural characterization of recombinant humanized type III collagen cold gel and its effects on the biological functions of HaCaT cells.
  20. Inhibition of the EBF1-ITGB8 Axis in Bone Marrow Niche Ameliorates Hallmarks of Myelofibrosis.
  21. Pre-antigenic regulatory signals in osteoarthritis: modulators of dendritic cell activation and joint immune balance.
  22. Establishment of a xenograft model of endometriosis-associated fibrosis using human immortalized endometrial stromal cells overexpressing HOXC8.
  23. Fibroblast-Derived ECM as a Donor-Specific Pro-Osteogenic Coating Surpassing ASC- and Osteoblast-Derived ECM.
  24. Developmental, but not Homeostatic, Collagen V Expression Regulates Mature Murine Supraspinatus Tendon Structure, Function, and Gene Expression.
  25. The Role of the Epidermal Growth Factor Receptor in Kidney Tubulointerstitial Fibrosis.
  26. Nanoscale opportunities in extracellular matrix mimicry.
  27. A novel paradigm for chronic subdural hematoma: regenerative medicine strategies targeting the pathological microenvironment.
  28. Ctenophore mesoglea: building a mucus-like body.
  29. Dynamic Changes of Extracellular Matrix in Sepsis: A Review.
  30. Study on the Antioxidant and Anti-Myocardial Fibrosis Effects of a Phenylpropanoid Compound (Xanthiumnolic C) Derived from Schisandra sphenanthera.
  31. Fibroblast-Targeted Nanodelivery Systems: Mechanisms of Collagen Remodeling Regulation and Novel Strategies for Scar Repair.
  32. Long Non-Coding RNA H19 mediates STAT3 dependent activation of keratinocytes and fibroblasts in Systemic Sclerosis skin.
  33. RUNX1 is a mediator of fibrotic activation and epigenetic memory in lung fibroblasts.
  34. Viral Pathogens and Pulmonary Fibrosis: EMT-Driven Mechanisms and Insights From Traditional Chinese Medicine.
  35. A New Bioprinted Dual-Layered Corneal Structure Using Collagen-Based Bioinks.
  36. Adipocytes as core drivers of skin aging and novel targets for regeneration.
  37. The Stiff Side of Cancer: How Matrix Mechanics Rewrites Non-Coding RNA Expression Programs.
  38. Targeted inhibition of RGS19 alleviates renal fibrosis by restoring autophagy and modulating immune cell infiltration.
  39. Vascular Destabilization and Pericyte Detachment are Mediated by hIAPP Aggregation in Transgenic Mice.
  40. Collagen from Marine Sources for Potential Application in Wound Treatment.
  41. Beyond the chaos: How architecture structures tumour biology.
  42. Molecular Mechanisms of Rotator Cuff Degeneration Identified by Spatial Transcriptomics and Multiplex Immunofluorescence.
  43. Nonlinear Microscopy of ECM Remodeling in Renal and Vascular Tissues: A Systematic Review Integrating Human AVF Imaging.
  44. TGF-β-induced fibrotic scar formation limits recovery of spinal cord injury.
  45. Ribosome heterogeneity and specialization in musculoskeletal physiology and pathology.
  46. Tetranectin and Paraoxonase-1 as Markers of Heart Failure.
  47. Brain-derived neurotrophic factor in age-related macular degeneration.
  48. Effect of type I collagen on TLR-3 induced MMP-13 expression in human periodontal ligament fibroblasts.
  49. FOXC2 regulates CYP1B1 transcription and activates the TGF-β/Smad pathway to promote pulmonary fibrosis.
  50. Targeting EIF5A suppresses liver fibrosis through impairment of mitochondrial function in hepatic stellate cells.
  1. J Cell Commun Signal. 2026 Mar;20(1): e70067
    Structural maintenance of chromosome protein 1A exacerbates liver fibrosis by enhancing hepatic stellate cell activation and extracellular matrix synthesis via laminin subunit gamma 2 activation.
    Dandan Wang, Ning Li, Ranyan Gao, Jiaxin Wang, Lingyi Xu, Fengchun Li, Xinyu Geng, Ram Prasad Chaulagain, Babalola Deborah Oluwaseun, Xiaoyu Zhang, Shuang Jin, Shizhu Jin.
      Liver fibrosis is characterized by an abnormal buildup of extracellular matrix (ECM), which is primarily produced by hepatic stellate cells (HSCs). Laminin subunit gamma 2 (LAMC2) is an ECM protein whose functional role in hepatic fibrosis remains to be fully elucidated. Herein, we examine how LAMC2 contributes to liver fibrosis and explore the molecular mechanisms in both animal and cellular models. LAMC2 was knocked down in C57BL/6J mice with CCl4-induced liver fibrosis. Rescue experiments were conducted in sh-LAMC2-treated and recilisib (PI3K/Akt agonist)-treated mice. The transcription factors associated with LAMC2 in liver fibrosis were predicted and verified. Transforming growth factor (TGF)-β1-stimulated LX-2 cells (HSC line) were infected with lentiviral vectors for in vitro assays. LAMC2, which was enriched in the PI3K/Akt pathway, was increased in the liver tissues of mice treated with CCl4, and recilisib reversed LAMC2 knockdown-mediated alleviation of liver fibrosis in these mice. LAMC2 transcription in activated HSCs was caused by structural maintenance of chromosome protein 1A (SMC1A). The inhibitory effect of SMC1A knockdown on ECM accumulation and HSC activation was mitigated by LAMC2 overexpression. This study provides new insights and highlights the promising potential of the SMC1A/LAMC2/PI3K/Akt axis as a therapeutic target for liver fibrosis.
    Keywords:  LAMC2; SMC1A; extracellular matrix accumulation; hepatic stellate cell; liver fibrosis
    DOI:  https://doi.org/10.1002/ccs3.70067
  2. Immun Inflamm Dis. 2026 Feb;14(2): e70361
    Deficiency of NF-Erythroid 2-Related Factor 2 Exacerbates the Scar Through ERK Signaling Pathway.
    Xueyuan Hao, Mengke Sun, Ruotong Wang, Hong Chen, Junkai Huang, Jing Luo, Haoyue Yu, Yingxi Li, Weibin Xing, Xiaoxia Li, Lizhi Hu.
       BACKGROUND: Scar, primarily composed of poorly structured and disordered collagen, is mainly characterized by excessive fibroblast activation and abnormal collagen deposition. Previous studies have shown that fibroblast activation is closely related to the imbalance of inflammatory responses and reactive oxygen species. NF-erythroid 2-related factor 2 (Nrf2) is an important transcription factor involved in regulating inflammation and oxidative stress. Although current evidence suggests that Nrf2 influences the occurrence of skin fibrosis, the role of Nrf2 in scar formation remains unknown.
    METHODS: In this study, we used qRT-PCR, Western Blot, and Immunohistochemical/Immunofluorescent staining to explore the role of Nrf2 in wound healing and scar formation.
    RESULTS: The deficiency of Nrf2 delayed the process of wound healing and exacerbated collagen deposition. Moreover, significant elevations in the mRNA expression of collagen synthesis-related genes were observed in Nrf2-deficient mice in vivo and in vitro. Meanwhile, Nrf2 deficiency also exacerbated inflammatory responses, leading to abnormal fibroblast activation and sustained activation of the ERK signaling pathway.
    CONCLUSION: These results suggest that Nrf2 plays a crucial role in fibroblast activation and scar formation, and our findings offer a novel therapeutic approach for reducing scar formation after skin injury.
    Keywords:  ERK signaling pathway; Nrf2; collagen; fibroblasts; scar formation
    DOI:  https://doi.org/10.1002/iid3.70361
  3. bioRxiv. 2026 Feb 19. pii: 2026.02.17.706476. [Epub ahead of print]
    WISP1 drives a mechanically active immune modulatory and proliferative cardiac myofibroblast state.
    Sharon Parkins, Sarah R Anthony, Teagan K Goldsworthy, Akanksha Nigam, Neva C Schehl, Robert M Jaggers, Daniel A Kasprovic, Lisa C Green, Onur Kanisicak, Michael Tranter.
      Pathological cardiac remodeling is driven by the proliferation and differentiation of resident fibroblasts into active myofibroblasts and results in excessive extracellular matrix (ECM) deposition and tissue stiffening. Expression of the matricellular protein WISP1 has previously been shown to be increased with cardiac fibrosis and promote myofibroblast activity, but the mechanisms by which this occurs remain unknown. Primary cardiac fibroblasts were isolated from adult mouse hearts and treated with recombinant WISP1 or TGFβ1 both alone and in combination to determine the functional role of the matricellular protein WISP1 in driving cardiac myofibroblast activity. WISP1 significantly increased alpha-smooth muscle actin and collagen type I expression, total collagen secretion, collagen gel contractility, and wound healing equally in fibroblasts from both male and female mice. However, WISP1 alone failed to induce expression of periostin, a hallmark myofibroblast marker, suggesting the resulting WISP1-dependent cell phenotype is unique and/or acting through non-canonical pathways. Indeed, inhibition of P38 MAPK completely ablated the WISP1-dependent increase in α SMA and collagen expression, while having little to no impact on TGFβ1-dependent expression of myofibroblast marker genes. We next employed a multi-omics approach to define the functional impact of WISP1 on fibroblast cell-state within the transcriptome, cytosolic, and secreted ECM proteome. RNA-seq results show that WISP1 broadly promotes the expression of proliferative and immune modulatory genes at the transcriptomic level, while having very little impact on traditional myofibroblast and ECM modifying gene expression programs. At the proteome level, WISP1 was again a much weaker mediator of traditional myofibroblast and ECM proteins. However, in agreement with RNA-seq data, we observed a strong WISP1-dependent enrichment for proliferation-associated proteins in the cytosolic proteome and inflammation-associated proteins in the ECM proteome. Interestingly, WISP1 also showed a context-dependent response with TGFβ1, suggesting a more complex and yet to be elucidated signaling interaction between these independent mediators of myofibroblast activity. In conclusion, our data suggests that WISP1 promotes a unique proliferative and immune-modulatory myofibroblast phenotype.
    Highlights: WISP1 is sufficient to drive myofibroblast α SMA and collagen expression and ECM deposition WISP1 promotes canonical myofibroblast contractility and wound healing activityWISP1 mediates myofibroblast activity via a non-canonical, P38 MAPK-dependent signaling pathwayMulti-omics analysis of WISP1-dependent RNA and protein expression show that WISP promotes a proliferative and immune modulatory myofibroblast phenotype.
    DOI:  https://doi.org/10.64898/2026.02.17.706476
  4. Cell Biochem Funct. 2026 Feb;44(2): e70188
    Adipose Tissue Extracellular Matrix Remodeling: A Driver of Obesity and Insulin Resistance.
    Imane Nait Irahal, Asmaa Chbel, Ayoub Lafnoune, Bouchra Darkaoui, Hicham Wahnou.
      This review explores the role of extracellular matrix (ECM) in adipose tissue highlighting its composition, regulation, and impact on obesity and insulin resistance. The ECM in adipocytes is a dynamic entity and highly organized network composed of structural proteins which provide mechanical support for cells and tissues and regulate cellular signaling. ECM modifiers, such as matrix metalloproteinases and tissue inhibitors of metalloproteinases, coordinate ECM remodeling to allow the expansion of adipocytes. Furthermore, ECM receptors like integrins and CD44 mediate adipocytes-microenvironment interactions, affecting the inflammatory process resulting in insulin resistance. The ECM components are posttranslational being modified by an array of remodeling enzymes, such as lysyl oxidase and prolyl-4-hydroxylase, to regulate ECM integrity. While excessive ECM deposition and fibrosis urge physical constraints on adipocyte expansion, ECM remodeling emerges as a denominator linking obesity and insulin resistance associated with vascular dysfunction and severe inflammation emphasizing the role of ECM in metabolic diseases.
    Keywords:  adipose tissue; extracellular matrix; insulin resistance; obesity; remodeling
    DOI:  https://doi.org/10.1002/cbf.70188
  5. Int J Mol Sci. 2026 Feb 07. pii: 1627. [Epub ahead of print]27(4):
    Serpine1 Regulates the Enhanced Inhibitory Effect of CHIR99021 Combined with Fibroblast Growth Factor 2 on Myocardial Fibrosis After Myocardial Infarction in Mice.
    Yangyang Jia, Xiangqin Tian, Mengyu Wei, Pingping Xu, Jikui Wang, Yaping Xu, Changye Sun, Zhikun Guo.
      Cardiac fibrosis is a pathological phenomenon caused by tissue remodeling and excessive matrix proliferation under stress conditions. CHIR99021 is a selective glycogen synthase kinase-3 inhibitor that has shown potential in cardiovascular regeneration therapy. Fibroblast growth factor 2 (FGF2) has a protective effect on ischemic myocardium. However, the effect and underlying mechanism of the combined use of CHIR99021 and FGF2 on myocardial fibrosis remains unclear. In this study, we found that the combination of CHIR99021 and FGF2 could significantly inhibit the activation of cardiac fibroblasts (CFs) and alleviate the formation of collagen scars in mouse myocardium. By analyzing the expression levels of fibrotic proteins, such as ColI, ColIII and alpha smooth muscle actin (α-SMA) in fibroblasts in vitro and in vivo, we confirmed the inhibitory effect of CHIR99021 combined with FGF2 on the activation of fibroblasts. Transcriptome sequencing showed that CHIR99021 and FGF2 inhibited the expression level of Serpine1 through the transforming growth factor-β (TGF-β) and Focal Adhesion Kinase (FAK) signaling pathways. By analyzing the regulatory effect of overexpressed and knocked-down Serpine1 on fibrotic pathway-related proteins in CFs, we verified that Serpine1 is a key target for inhibiting fibrosis. In conclusion, this study provides evidence that Serpine1 may be a potential mechanism that enables CHIR99021 combined with FGF2 to improve myocardial fibrosis.
    Keywords:  CHIR99021; FGF2; Serpine1; cardiac fibroblasts; cardiac fibrosis
    DOI:  https://doi.org/10.3390/ijms27041627
  6. Front Immunol. 2026 ;17 1765095
    ECM remodeling-associated immune signatures and hub proteins: predictive markers and therapeutic targets for metastatic gastric cancer.
    Xinyue Hu, Kai Zhao, Yaoqiang Shi, Zhongjian Liu, Yi Sun.
       Background: Gastric cancer (GC) remains one of the most prevalent malignancies worldwide. A growing number of studies have identified the extracellular matrix (ECM) as a key regulator in gastric cancer development and metastasis. Gastric cancer cells interact with the ECM, modifying its composition and structure, thereby promoting tumor invasiveness and metastatic ability. However, the specific molecular mechanisms underlying these processes remain poorly understood.
    Methods: In this study, we identified metastasis-related hub proteins in the extracellular matrix by proteomics, explored the differentiation trajectories of tumor cells at the single-cell levelidentified metastasis-related trajectories and metastasis-associated tumor cell subtypes, and experimentally verified the roles and mechanisms by which metastasis-associated ECM proteins regulate the migration and invasion of gastric cancer cells.
    Results: Our proteomic analysis revealed 282 prognosis-related differential proteins between gastric cancer metastasis-free and metastasis-associated groups, including 77 extracellular matrix proteins. We constructed a protein-protein interaction (PPI) network and identified four core hub proteins using network centrality measures. Single-cell RNA sequencing provided a detailed landscape of gastric cancer cells, enabling exploration of the expression patterns of these hub proteins across different cell subtypes. Trajectory analysis uncovered distinct pathways associated with tumor metastasis and highlighted the regulatory roles of hub proteins in this process. We identified two key tumor cell subtypes critical for metastasis, and through cell communication analysis, identified significantly enriched pathways linked to metastatic progression. In vitro experiments further validated the functional role of Ribosomal Protein S29(RPS29) in the metastatic mechanisms of gastric cancer cells.
    Conclusion: This study not only reveals the complexity of ECM remodeling in the microenvironment of gastric cancer but also provides new perspectives and potential targets for future gastric cancer treatment and brings opportunities for the development of new therapeutics, which are expected to overcome the challenge of cancer metastasis.
    Keywords:  extracellular matrix (ECM); gastric cancer; metastasis; single-cell RNA sequencing; tumor
    DOI:  https://doi.org/10.3389/fimmu.2026.1765095
  7. Front Immunol. 2026 ;17 1765221
    PHLDA1 is a shared diagnostic and key mediator of inflammatory fibrosis in heart and kidney.
    Lei Hua, Liangru Shen, Yongshou Tao, Chentong Wang, Xiaohang Shao.
       Background: Inflammation-driven fibrosis represents a common pathological endpoint in both heart failure (HF) and chronic kidney disease (CKD), which together affect over 1 billion people worldwide. Understanding the shared molecular mechanisms by which inflammation contributes to the pathogenesis of HF and CKD is crucial for enabling early diagnosis and guiding the development of broad-spectrum therapeutic strategies.
    Methods: Utilizing multi-omics technologies and machine learning algorithms, we performed an integrative analysis of HF and CKD samples to uncover shared mechanisms underlying inflammation-induced fibrosis. Furthermore, key regulators identified through bioinformatic analysis were experimentally validated using primary cell co-culture assays, gene knockout approaches, and bulk RNA sequencing.
    Results: Single-nucleus RNA sequencing (snRNA-seq) revealed concurrent upregulation of IL-1β and Pleckstrin Homology-Like Domain Family A Member 1 (PHLDA1) in both cardiac M1 macrophages and injured proximal tubular epithelial (PTE) cells. PHLDA1 promotes IL-1β expression and the knockout of PHLDA1 suppressed NF-κB signaling and renal fibrosis. Administration of IL-1β induced PHLDA1 expression in cardiac fibroblasts and renal PDGFRβ+ cells, suggesting a positive feedback loop that contributes to fibrosis.
    Conclusions: In this study, we identified PHLDA1 as a key driver of fibrosis in both the heart and kidney, acting through IL-1β mediated intercellular crosstalk. These findings indicate PHLDA1 as a potential therapeutic candidate for mitigating fibrosis in cardio-renal syndrome.
    Keywords:  IL-1β; PHLDA1; fibrosis; heart-kidney; intercellular crosstalk
    DOI:  https://doi.org/10.3389/fimmu.2026.1765221
  8. Cell Tissue Res. 2026 Feb 23. pii: 25. [Epub ahead of print]403(2):
    Interleukin-4 changes the transcriptome, ECM-associated components and function of mare endometrial fibroblast: Insights from healthy and fibrotic cells.
    Anna Wójtowicz, Agnieszka Sadowska, Kamil Myszczyński, Tomasz Molcan, Monika M Kaczmarek, Anna Szóstek-Mioduchowska.
      Fibrosis remains incompletely understood, particularly in terms of how immune mediators shape stromal programs. We used a spontaneous large‑animal model-endometrosis (equine endometrial fibrosis) to define how interleukin‑4 (IL‑4) reprograms fibroblasts from healthy and fibrotic endometrium. Primary fibroblasts were exposed to IL‑4 (10 ng/mL) for 48 or 96 h. At 48 h, bulk transcriptomes revealed 1307 differentially expressed genes (DEGs; 648 up, 659 down) and 1271 DEGs (645 up, 626 down) in fibroblasts derived from endometria without or with endometrosis, respectively. Enrichment analyses implicated cellular metabolism, extracellular matrix (ECM) organization and remodeling, and signaling pathways commonly linked to fibrogenesis. IL‑4 also affected the long non‑coding RNA (lncRNA) expression, with 143 and 135 differentially expressed lncRNAs in fibroblasts derived from healthy or fibrotic endometria, respectively; linking these lncRNAs to DEGs involved in inflammation, ECM organization, and cytokine signaling. Moreover, IL‑4 increased proliferation and viability in fibroblasts derived from healthy or fibrotic endometria, while selectively reducing migration in fibroblasts derived from endometria without fibrosis after 96 h. IL‑4 further altered mRNA expression, protein abundance, and gelatinolytic activity of matrix metalloproteinases in a manner contingent on the fibrosis status of the tissue of origin, indicating stage‑dependent control of ECM turnover. Collectively, these data identify IL‑4 as a potent modulator of fibroblast function in a spontaneous large‑animal fibrosis model, revealing fibrosis stage‑dependent responses.
    Keywords:  Endometrosis; Extracellular matrix; Fibrosis; Interleukin 4; Mare; Remodeling
    DOI:  https://doi.org/10.1007/s00441-026-04049-6
  9. Int J Mol Sci. 2026 Feb 19. pii: 1999. [Epub ahead of print]27(4):
    Prolyl 3-Hydroxylase 2 Supports a Pro-Angiogenic Milieu Promoting Colorectal Cancer Progression and Metastasis.
    Sonia Panico, Antonio Adinolfi, Sara Magliacane Trotta, Luca D'Orsi, Grazia Mercadante, Andrea Paradisi, Patrick Mehlen, Valeria Tarallo, Sandro De Falco.
      Prolyl 3-hydroxylase 2 (P3H2) is a key enzyme involved in the architecture of the extracellular matrix (ECM). While previously shown to be regulated by VEGF-A and to play a role in angiogenesis, its function in cancer remains ambiguous. While characterized as a tumor suppressor, its precise function in colorectal cancer (CRC) progression is poorly defined. Bioinformatic analysis and patient data reveal that P3H2 transcript levels are significantly reduced in colon adenocarcinoma tissues, showing a progressive decline in metastatic lesions. Furthermore, VEGF-A exposure upregulates P3H2 transcripts in the HCT116 CRC cell line. To investigate its impact in CRC, we generated a stable HCT116 clone overexpressing P3H2. In vitro studies demonstrated that while P3H2 overexpression inhibited anchorage-independent growth, it significantly enhanced cellular invasion without altering cell proliferation. In vivo, however, P3H2-overexpressing tumors exhibited accelerated tumor growth and a statistically significant increase in lung metastases. P3H2 overexpression remodeled the tumor microenvironment (TME) by modifying its main substrate, Collagen IV, resulting in the induction of increased vessels density. Our study repositions P3H2 as a dynamic enzymatic switch within the TME. This work identifies P3H2-driven ECM remodeling as a promising therapeutic axis in advanced CRC, with particular relevance for combination strategies targeting angiogenesis.
    Keywords:  Prolyl 3-hydroxylase 2; angiogenesis; colorectal cancer
    DOI:  https://doi.org/10.3390/ijms27041999
  10. In Vivo. 2026 Mar-Apr;40(2):40(2): 923-932
    Ferrochel Alleviates Renal Fibrosis by Modulating Fibrogenesis and Epithelial-to-Mesenchymal Transition: In Vitro and In Vivo Studies.
    Chien-Hsing Lee, Wei-Liang Chen, Wen-Hua Lin, Yi-Hsuan Ting, Tung-Wei Hung, Yi-Hsien Hsieh.
       BACKGROUND/AIM: Ferrochel consists of one ferrous ion chelated with two glycine molecules and is characterized by high bioavailability and physiological activity. However, its potential anti-fibrotic effects and underlying mechanisms remain need clarified. The aim of this study was to determine whether Ferrochel exerts anti-fibrotic activity in renal fibrosis and to clarify the mechanisms by which it may regulate fibrosis and epithelial-mesenchymal transition.
    MATERIALS AND METHODS: A mouse renal tubulointerstitial fibrosis model was established by applying unilateral ureteral obstruction (UUO). Renal morphology, collagen deposition, and iron content were evaluated using hematoxylin and eosin (H&E) staining and Masson's trichrome staining. The expression of fibrosis- and epithelial-mesenchymal transition (EMT)-related proteins was assessed using immunohistochemistry (IHC) and immunoblotting. Cytotoxicity and cell motility were examined using the MTT assay and wound healing assay, respectively.
    RESULTS: Ferrochel treatment significantly reduced collagen deposition and renal injury in UUO mice without inducing iron accumulation. Moreover, Ferrochel reduced the expression of fibrosis markers (α-SMA and collagen I) and the EMT marker vimentin in the UUO model. In HK2 cells, Ferrochel did not exhibit cytotoxicity. However, it markedly attenuated transforming growth factor-beta1 (TGF-β1)-induced cell motility and decreased the expression of fibrosis markers (α-SMA and collagen I) as well as the EMT marker vimentin in TGF-β1-treated HK2 cells.
    CONCLUSION: Ferrochel attenuated renal fibrogenesis and EMT in vitro and in vivo, indicating anti-fibrotic activity. These results suggest that Ferrochel may serve as a potential therapeutic agent for renal tubulointerstitial fibrosis.
    Keywords:  EMT; Ferrochel; UUO; renal tubulointerstitial fibrosis
    DOI:  https://doi.org/10.21873/invivo.14248
  11. Br J Dermatol. 2026 Feb 23. pii: ljag068. [Epub ahead of print]
    Microbiota-fibroblast crosstalk represents the missing link in skin barrier dysfunction and fibrosis.
    Zhen Lin, Lan Yang, Yiwen Han, Caiyu Qi, Lu Chen, Yuxuan Luo, Yihan Lin, Evan Sweren, PeiYang Chen, Martin P Alphonse, Luis A Garza, Gaofeng Wang.
      Dermal fibroblasts are key cellular components of the skin stroma, primarily responsible for extracellular matrix synthesis and maintenance of tissue structure and function. Beyond this canonical role, these cells also possess immune regulatory functions, enabling them to sense and integrate microbial cues to orchestrate cutaneous inflammatory responses, wound repair, and fibrogenesis. The skin microbiome is a critical regulator of fibroblast homeostasis; its dysbiosis disrupts fibroblast-microbe crosstalk, leading to aberrant fibroblast activation and contributing to the pathogenesis of various dermatological conditions. Clinically, the burden of these disorders is substantial, and current therapeutic strategies targeting fibroblast dysfunction often yield limited efficacy. Fortunately, recent advances in deciphering the pathophysiological mechanisms underlying fibroblast-microbe interactions have highlighted critical molecular regulatory networks, opening new therapeutic avenues. Among these emerging approaches, interventions targeting the microbiota-fibroblast axis-such as probiotics, postbiotics, and fibroblast-directed agents-hold considerable promise. Deciphering the nuances of this crosstalk is pivotal for advancing precision, regenerative therapies, with potential implications for both cutaneous and systemic fibrotic disorders.
    DOI:  https://doi.org/10.1093/bjd/ljag068
  12. Int J Mol Sci. 2026 Feb 20. pii: 2017. [Epub ahead of print]27(4):
    The Fibro-Immune Landscape Across Organs: A Single-Cell Comparative Study of Human Fibrotic Diseases.
    Guofei Deng, Yusheng Luo, Xiaorong Lin, Yuzhi Zhang, Yuqing Lin, Yuxi Pan, Yueheng Ruan, Xiaocong Mo, Shuo Fang.
      Fibrosis is a hallmark of the tumor microenvironment in many solid cancers, driving tumor progression, immune evasion, and treatment resistance; however, the molecular and cellular mechanisms underlying fibrogenesis-particularly stromal-immune crosstalk across organs-remain incompletely understood, compounded by organ-specific heterogeneity and a lack of reliable immune-related biomarkers. To address this, we performed an integrative single-cell RNA sequencing (scRNA-seq) analysis of fibrotic tissues from four major organs-liver, lung, heart, and kidney-alongside non-fibrotic controls, applying unsupervised clustering, trajectory inference, cell-cell communication modeling, and gene set variation analysis (GSVA) to map the fibro-immune landscape. Our analysis revealed both conserved and organ-specific features: fibroblasts were the dominant extracellular matrix (ECM)-producing cells in liver and lung, whereas endothelial-derived stromal populations prevailed in heart and kidney. Immune profiling uncovered distinct infiltration patterns-macrophages displayed organ-specific polarization states; T cells were enriched for tissue-resident subsets in lung and mucosal-associated invariant T (MAIT) cells in liver; and B cells exhibited marked heterogeneity, including a pathogenic interferon-responsive subset prominent in pulmonary fibrosis. GSVA further identified divergent signaling programs across organs and lineages, including TGF-β/TNF-α in the heart, NOTCH/mTOR in the kidney, glycolysis/ROS in the lung, and KRAS/interferon pathways in the liver. Cell-cell communication analysis highlighted robust crosstalk between macrophages, T/B cells, and stromal cells mediated by collagen, laminin, and CXCL signaling axes. Together, this cross-organ atlas delineates a highly heterogeneous fibro-immune ecosystem in human fibrotic diseases, revealing shared mechanisms alongside organ-specific regulatory networks, with immediate translational implications for precision anti-fibrotic therapy, immunomodulatory drug repurposing, and the development of context-specific biomarkers for clinical stratification and therapeutic monitoring.
    Keywords:  anti-fibrotic therapies; fibrosis; organ specificity; single-cell RNA sequencing; stromal–immune crosstalk
    DOI:  https://doi.org/10.3390/ijms27042017
  13. Clin Transl Oncol. 2026 Feb 27.
    Unravelling the pathogenesis and therapeutic approaches of pancreatic ductal adenocarcinoma.
    Isha Roy, Raman Thakur.
      Pancreatic ductal adenocarcinoma (PDAC) is one of the aggressive cancers having high metastasis, late progression and resistance to therapies. PDAC arises from the ductal epithelium of the pancreas. The tumour microenvironment plays a key role in metastasis. One of the reasons behind PDAC being so aggressive as a cancer is that it forms a dense stroma around the neoplastic epithelium, which contributes to further tumour progression, invasion, metastasis and drug resistance. The key components of PDAC include the extracellular matrix (ECM), cancer-associated fibroblasts (CAFs) and vasculature. The dense stroma in the ECM prevents drug penetration into cancer cells, making PDAC more challenging to treat. The oncogenic KRAS mutation is mainly responsible for the initiation, progression, immune evasion and further therapy resistance in this cancer. Despite having a low rate of survival, therapies available for this cancer are now emerging and developing rapidly. There are many more therapies now available for the treatment of PDAC, including immunotherapies, targeted gene therapies, stroma-targeting therapies and novel chemotherapies, which are much more promising in this cancer. This article focuses on the pathogenesis of PDAC and the various recent therapies used to treat it. It further discusses future perspectives in the treatment of this cancer, AI-driven therapies and challenges in this field.
    Keywords:  CAFs; Immunotherapies; KRAS gene; Pancreatic cancer
    DOI:  https://doi.org/10.1007/s12094-026-04289-6
  14. Front Biosci (Landmark Ed). 2026 Feb 06. 31(2): 46251
    LXN-THBS2 Signaling Axis Regulates Hepatic Stellate Cell Activation and Promotes the Development of Liver Fibrosis.
    Haoyan Wang, Hanyu Jiang, Suyi Wang, Xinru Luo, Xi Tan, Donglin Cao, Yachao Yao.
       BACKGROUND: Liver fibrosis, the end-stage pathological state of many liver diseases, is primarily driven by the activation of hepatic stellate cells (HSCs) and collagen deposition resulting from various pathogenic causes. Thrombospondin-2 (THBS2), a secreted extracellular matrix glycoprotein encoded by the TSP gene family, has been found to activate the TLR4-transforming growth factor-β (TGF-β)/FAK signaling axis and HSCs through autocrine signalling, thereby contributing to the development of liver fibrosis. Latexin (LXN), the only known zinc-dependent metallocarboxypeptidase inhibitor in humans, has not yet been studied for its role in liver fibrosis is yet to be studied.
    METHODS: In this study, we used adeno-associated virus 9 (AAV9) to generate a mouse model of liver fibrosis with LXN knockdown and used siLXN to knock down the LXN gene in the human hepatic stellate cell line LX-2. The mechanisms underlying the association between LXN and hepatic fibrosis progression were investigated using quantitative polymerase chain reaction, western blot, immunohistochemistry, and immunofluorescence staining.
    RESULTS: LXN knockdown reduced carbon tetrachloride (CCl4)-induced liver injury and suppressed activation of hepatic stellate cells, while also inhibiting the expression of α-SMA and collagen I. Furthermore, LXN demonstrates a substantial positive correlation with THBS2, and LXN knockdown was capable of downregulating THBS2.
    CONCLUSION: The LXN-THBS2 signaling axis may promote liver fibrosis progression by inducing the activation of HSCs.
    Keywords:  LXN; THBS2; cirrhosis; hepatic stellate cells; liver fibrosis
    DOI:  https://doi.org/10.31083/FBL46251
  15. Cells. 2026 Feb 16. pii: 354. [Epub ahead of print]15(4):
    Adventitial Fibrosis and Fibroblast Mechanosensitivity Are Shaped by Sex and Hormonal Status in Pulmonary Arterial Hypertension.
    Yufan Lin, Ariel Wang, Daniela Valdez-Jasso.
      Pulmonary arterial hypertension (PAH) is marked by vascular remodeling, yet the role of adventitial fibrosis-and its modulation by sex and hormonal status-remains unclear. We examined stage-specific adventitial remodeling and pulmonary artery adventitial fibroblast (PAAF) mechanosensitivity in male, ovary-intact female, and ovariectomized (OVX) female Sprague-Dawley rats with SuHx-induced PAH. Hemodynamics, pulmonary artery histology, and adventitia-specific transcriptional profiling were integrated with in vitro assays of PAAFs exposed to defined substrate stiffness and stretch. All groups developed comparable increases in mean pulmonary arterial pressure, but vascular resistance shift and adventitial fibrosis diverged by sex: intact females showed attenuated increase in pulmonary vascular resistance and transient collagen accumulation, whereas OVX females mirrored the sustained, male-like progression. Extracellular matrix (ECM) gene activation occurred without smooth muscle actin induction, suggesting noncanonical fibrotic pathways. In vitro, intact female PAAFs required higher substrate stiffness to induce profibrotic gene expression, indicating a hormone-modulated stiffness threshold. OVX PAAFs showed persistent transcriptional reprogramming, while stretch-induced ECM upregulation occurred predominantly in male-derived PAAFs. These findings demonstrate that adventitial fibrosis in PAH is shaped by both hormonal and chromosomal sex, independent of hemodynamic severity, and highlight fibroblast mechanosensitivity as a potential target for stage- and sex-specific interventions.
    Keywords:  fibroblast; gene expression; pulmonary arterial adventitia; pulmonary arterial hypertension; sex differences
    DOI:  https://doi.org/10.3390/cells15040354
  16. Life Sci. 2026 Feb 24. pii: S0024-3205(26)00101-3. [Epub ahead of print] 124292
    The Tet3 degrader Bobcat339 ameliorates isoprenaline induced cardiac fibrosis and heart failure: animal and transcriptomic studies.
    Shuai Liu, Minhui Ding, Yuanyuan Zhang.
       AIMS: Aberrant cardiac fibrosis contributes to heart failure. It has been previously shown that the DNA dioxygenase ten-and-eleven translocator 3 (TET3) promotes cardiac fibrosis and heart failure. In the present study we examined the effects of a small-molecule TET3 degrader Bobcat339 on cardiac fibrosis and cellular transcriptome.
    METHODS AND MATERIALS: C57BL/6J mice were injected with isoprenaline (ISO) to induce cardiac fibrosis and heart failure. Cellular transcriptome was evaluated by RNA-seq and ATAC-seq.
    KEY FINDINGS: Co-treatment with Bobcat339 significantly attenuated activation of cardiac fibroblasts subjected to ISO treatment. Compared to the mice injected with vehicle control, the mice injected with Bobcat339 displayed significantly amelioration of cardiac fibrosis as evidenced by histological staining, hydroxyproline levels, and expression of myofibroblast markers in the heart. Intervention with Bobcat339 rescued the mice from ISO-induced heart failure but did not influence cardiac hypertrophy. RNA-seq data indicated that Bobcat339 intervention led to massive transcriptomic alterations in cardiac fibroblasts. These changes could be attributed to, at least in part, by differential chromatin accessibility as uncovered by ATAC-seq. An integrated analysis of RNA-seq and ATAC-seq suggested that Bobcat339 primarily impacted genes regulating extracellular matrix and cytoskeletal remodeling.
    SIGNIFICANCE: Our data demonstrate that Bobcat339 antagonizes ISO-induced cardiac fibrosis in mice thus affirming that TET3 could be targeted for the intervention of heart failure. In addition our data shed additional light on the mechanism whereby TET3 contributes to activation of cardiac fibroblasts to promote cardiac fibrosis and heart failure.
    Keywords:  Cardiac fibroblast; Cardiac fibrosis; Heart failure; Transcriptional regulation; Translational medicine
    DOI:  https://doi.org/10.1016/j.lfs.2026.124292
  17. Res Sq. 2026 Feb 19. pii: rs.3.rs-8817797. [Epub ahead of print]
    N-Cadherin Dynamically Regulates Schwannoma Migration and Represents a Novel Therapeutic Target in NF2-Related Schwannomatosis.
    Yin Ren, Han Nguyen, Melanie Fisher, Ruiqi Zhou, Taha Jan.
      NF2-related schwannomatosis (NF2-SWN) is a devastating tumor predisposition syndrome marked by multiple schwannomas and substantial morbidity. Vestibular Schwannoma (VS), the hallmark tumor, causes deafness, vertigo and potentially fatal brainstem compression. A subset develops brainstem adhesions, making surgery - the only treatment option - highly risky in the absence of FDA-approved therapies. During NF2-SWN progression, schwannoma cells migrate from the extracellular matrix (ECM)-rich internal auditory canal to the arachnoid-lined brainstem, yet mechanisms driving this transition remain incompletely defined. We previously demonstrated that adherent schwannoma is associated with elevated matrix metalloproteinase-9 (MMP-9) activity. N-cadherin (N-cad), a key cell-matrix adhesion molecule and regulator of cancer cell migration, has not been studied in NF2-SWN. Integrating RNA sequencing, multiple NF2 schwannoma mouse models and primary human VS cultures, we demonstrate that N-cad is overexpressed in sporadic and NF2-associated VS. N-cad differentially regulates VS spheroid migration - promoting motility on astrocytes but restraining on ECM. MMP-9 cleaves N-cad to drive schwannoma proliferation through IL-6/STAT3 and NF-κB signaling. Pharmacologic and genetic inhibition of N-cad synergized with dasatinib and brigatinib, two kinase inhibitors with efficacy in NF2-SWN, to suppress schwannoma proliferation and tumor growth. These findings establish N-cad as a central regulator of schwannoma migration and a novel therapeutic target.
    DOI:  https://doi.org/10.21203/rs.3.rs-8817797/v1
  18. Cell Signal. 2026 Feb 24. pii: S0898-6568(26)00098-7. [Epub ahead of print] 112448
    CACNB2 overexpression suppresses atrial fibroblast activation and atrial fibrosis to mitigate atrial fibrillation.
    Dan Zhang, Zongjuan Li, Nijina Li, Hao Zhang.
      Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased morbidity and mortality due to complications such as stroke and heart failure. Cardiac fibrosis creates a pathological substrate for AF and remains inadequately addressed by current therapies. The calcium channel subunit CACNB2 has emerged as an underlying regulator of cardiac electrophysiology and fibrosis, yet its effects in the context of AF and atrial fibrosis remain poorly understood. In this study, CACNB2 was identify as a novel anti-fibrotic target in AF, demonstrating that CACNB2 overexpression in a rat AF model significantly improved electrophysiological parameters, including normalization of atrial effective refractory period (AERP), reappearance of regular P waves, and shortened AF duration, and mitigated atrial fibrosis and inflammation by reducing α-SMA, collagen I, and collagen III expression and inflammatory cytokine levels. In vitro, CACNB2 overexpression attenuated the profibrotic effects of Ang II on primary atrial fibroblasts, including reductions in cell viability and fibrotic marker expression. Also, CACNB2 overexpression modulated calcium handling and cellular oxidative stress responses in primary atrial cardiomyocytes under Ang II stimulation. This protective effect was accompanied by a modulation of the TGF-β/Smad pathway, suggesting a direct regulatory effect of CACNB2 on this fibrotic process. Collectively, our findings reveal that CACNB2 overexpression plays a protective role against AF and cardiac fibrosis by improving electrophysiological stability, reducing fibrotic remodeling, and modulating fibroblast and cardiomyocytes phenotype and function. These results highlight the novel therapeutic potential of targeting CACNB2 to treat AF and prevent its progression by addressing the underlying atrial fibrosis, offering a promising avenue for future research and development of novel AF therapies.
    Keywords:  Atrial fibrillation (AF); Atrial fibroblast; Atrial fibrosis; CACNB2; The TGF-β/Smad signaling pathway
    DOI:  https://doi.org/10.1016/j.cellsig.2026.112448
  19. Front Med (Lausanne). 2026 ;13 1749460
    Structural characterization of recombinant humanized type III collagen cold gel and its effects on the biological functions of HaCaT cells.
    Yizhe Wang, Sibin Kuang, Yuhui Fan, Danfeng Li, Ling Li, Jian Wang, Wei Bian.
      Recombinant humanized collagen has been widely used in the biomedical field. This study focuses on the characterization of a novel recombinant humanized type III collagen cold gel (C3Gel). To verify the structural integrity of C3Gel and explore its in vitro cytocompatibility and potential biological applications, a multi-technique approach covering composition, structure, thermal properties, and morphology was employed to perform comprehensive structural analysis. In addition, in vitro biological functional assessments were conducted using cell-based assays. The results demonstrated that the molecular weight and structural sequence of C3Gel were consistent with theoretical expectations. Under low-temperature conditions, C3Gel self-crosslinked into a porous network structure and exhibited favorable cytocompatibility. It enhanced the microenvironment of the extracellular matrix (ECM) and offered substantial structural support to HaCaT cells, which in turn facilitated their adhesion, proliferation, and migration. These findings suggest that C3Gel holds promise as a novel functional biomedical material, providing a scientific basis for further research and application of this recombinant collagen.
    Keywords:  C3Gel; cryo-electron microscopy; keratinocytes; thermal stability; triple helix; wound healing
    DOI:  https://doi.org/10.3389/fmed.2026.1749460
  20. bioRxiv. 2026 Feb 17. pii: 2026.02.16.706171. [Epub ahead of print]
    Inhibition of the EBF1-ITGB8 Axis in Bone Marrow Niche Ameliorates Hallmarks of Myelofibrosis.
    Lyudmila Tsurkan, Mélodie Douté, Nicholas Morchel, Lahiri Konada, Rashid Mehmood, Te Ling, Amha Atakilit, Bridget Marcellino, Ronald Hoffman, Peter Vogel, Dean Sheppard, John D Crispino, Marta Derecka.
      Fibrotic remodeling of the bone marrow (BM) niche is a characteristic feature of myelofibrosis (MF) that contributes to disease progression. In MF, mesenchymal stromal cells (MSCs) produce excessive amounts of inflammatory cytokines and extracellular matrix, leading to BM fibrosis, impaired blood production, extramedullary hematopoiesis, and progressive BM failure. While the genetic events that initiate MF in hematopoietic cells are well defined, our understanding of the mechanisms responsible for BM fibrosis remains incomplete. Here, we show that transcription factor EBF1 is a key regulator of the fibrotic gene program in mouse and human MSCs. EBF1 is upregulated in pre-fibrotic MSCs, while mice with MSC-specific deletion of Ebf1 exhibit reduced BM fibrosis, decreased expansion of myeloid cells and splenomegaly when transplanted with hematopoietic progenitors harboring the MF driver mutation MPL W515L . Moreover, we identify ITGB8 as an EBF1-regulated gene with therapeutic potential. MF mice treated with ITGB8-neutralizing antibodies or with MSC-specific Itgb8 deletion show reduced disease burden, as indicated by decreased marrow fibrosis, significantly reduced frequencies of MPL mutant cells, and reduced inflammation in the BM. Our data indicate that targeting the EBF1-ITGB8 axis in the MF MSCs may have therapeutic benefits.
    DOI:  https://doi.org/10.64898/2026.02.16.706171
  21. Front Immunol. 2026 ;17 1749150
    Pre-antigenic regulatory signals in osteoarthritis: modulators of dendritic cell activation and joint immune balance.
    Jiabao Liang, Andrew Mark Jackson.
      Osteoarthritis (OA) is now recognized as an immune-metabolic disorder rather than a simple wear-and-tear disease. Dendritic cells (DCs) in the synovium and subchondral bone link mechanical, biochemical, and metabolic stress to immune imbalance. In the early stage of immune activation, pre-antigenic regulatory signals act before classical antigen presentation and influence how DCs shape joint immunity. Increased extracellular matrix (ECM) stiffness activates the Integrin-FAK-NF-κB pathway, driving inflammatory or exhausted DC states. ECM fragments and damage-associated molecular patterns (DAMPs) stimulate pattern recognition receptors (PRRs), inducing cytokines that sustain chronic inflammation. Hypoxia, lactate, and oxidative stress reprogram DC metabolism, suppress IL-12, and promote Th17 responses. Targeting these upstream factors offers new therapeutic opportunities. Strategies that modify matrix stiffness, block DAMP-mediated signaling, or restore metabolic balance can help reset DC function and preserve joint homeostasis. Emerging biomaterial-based approaches further provide a foundation for immune-restorative and regenerative therapies. In the future, integrating DC-modulatory materials with personalized immune profiling may enable precise immuno-regenerative treatments for OA, representing a shift from symptom relief to immune-guided cartilage repair.
    Keywords:  damage-associated molecular patterns; dendritic cells; extracellular matrix stiffness; hypoxia; immuno-regenerative therapy; metabolic stress; osteoarthritis; pre-antigen regulatory signals
    DOI:  https://doi.org/10.3389/fimmu.2026.1749150
  22. Sci Rep. 2026 Feb 27.
    Establishment of a xenograft model of endometriosis-associated fibrosis using human immortalized endometrial stromal cells overexpressing HOXC8.
    Hitomi Takasaki-Kawasaki, Shun Sato, Tetsuro Tamehisa, Toshihide Yoneda, Amon Shiroshita, Taishi Fujimura, Isao Tamura, Ryo Maekawa, Norihiro Sugino.
      Endometriosis is a disease characterized by fibrosis and adhesions. There are still no treatment methods targeting these conditions. One reason for this is the lack of useful animal models to investigate the mechanisms of fibrosis and adhesion in endometriosis. We previously proposed that Homeobox C8 (HOXC8) acts as an upstream regulator involved in endometriosis development, promoting fibrosis by activating transforming growth factor β (TGFB) signaling in vitro. This study was undertaken to establish a xenograft mouse model for endometriosis-associated fibrosis using HOXC8-overexpressing cells. Stable lines of immortalized human endometrial stromal cells overexpressing HOXC8 (HOXC8-imESCs) and mock control lines (Control-imESCs) were established and evaluated for cellular functions in vitro. These cell lines were then transplanted under the renal capsule of severely immunodeficient mice, and the xenografts were harvested five weeks after transplantation. In vitro, cell migration, invasion, and fibrotic capacity were enhanced in HOXC8-imESCs compared to Control-imESCs. In the xenografts, HOXC8-imESCs exhibited significant collagen fiber production compared to Control-imESCs. Additionally, immunohistochemistry of the xenografts detected phosphorylated SMAD2/3 exclusively in HOXC8-imESCs, indicating that HOXC8 overexpression activates the TGFB/SMAD pathway aberrantly in vivo. In this study, a new animal model for endometriosis-associated fibrosis was established using the HOXC8-imESC xenograft model system.
    Keywords:  Endometrial stromal cells; Endometriosis; Fibrosis; HOXC8; TGFB/SMAD pathway; Xenograft model
    DOI:  https://doi.org/10.1038/s41598-026-41956-8
  23. J Funct Biomater. 2026 Feb 14. pii: 97. [Epub ahead of print]17(2):
    Fibroblast-Derived ECM as a Donor-Specific Pro-Osteogenic Coating Surpassing ASC- and Osteoblast-Derived ECM.
    Kevin Arnke, Hans-Christoph Pape, Paolo Cinelli.
      Large bone defects remain a major clinical challenge, as current treatments primarily provide mechanical stability while often insufficiently addressing the biological microenvironment. The cell-deposited extracellular matrix (CD-ECM) represents a promising strategy to improve implant bioactivity by mimicking key features of the native tissue. In this study, we compared CD-ECMs from adipose tissue-derived mesenchymal stromal cells (ASCs), ASC-derived osteoprogenitor cells, and dermal fibroblasts. ECM composition was analyzed, and its ability to support the osteogenesis of reseeded skeletal stem cells (SSCs) was assessed. Subsequently, the best performing cells were used to produce CD-ECM on a 3D scaffold. Furthermore, we improved the ECM by treating the ECM-producing cells with dextran sulfate (Dx-S). Fibroblast-derived ECM showed higher collagen and glycosaminoglycan contents compared to ASC-ECM or osteoprogenitor-ECM. Furthermore, only the fibroblast-derived ECM (Fibro-ECM) exerted a supportive effect on the osteogenesis of SSCs. SSCs seeded on ECM showed a higher proliferation rate and enhanced osteogenesis. Supplementation with dextran sulfate further increased ECM deposition and osteogenic potential. We showed that fibroblasts produced substantially more ECM with a stronger pro-osteogenic effect than ASCs or osteoprogenitor cells. The ECM and its pro-osteogenic effect could further be increased when fibroblasts were treated with Dx-S. Together, these results highlight Fibro-ECM as a promising and easily accessible cell-derived ECM deposition strategy to improve the biological performance of implants in bone regeneration.
    Keywords:  biomaterial coating; bone regeneration; cell-derived ECM; fibroblast-derived ECM; osteogenic differentiation
    DOI:  https://doi.org/10.3390/jfb17020097
  24. J Orthop Res. 2026 Feb;44(2): e70164
    Developmental, but not Homeostatic, Collagen V Expression Regulates Mature Murine Supraspinatus Tendon Structure, Function, and Gene Expression.
    Michael S DiStefano, Jeremy D Eekhoff, Stephanie N Weiss, Courtney A Nuss, Rebecca L Betts, Andrew F Kuntz, Louis J Soslowsky.
      The development of tendon hierarchical structure is dependent on collagen I assembly into fibrils and higher-order assemblies, a process regulated by interactions involving collagen V, a quantitatively minor yet essential component of the tendon extracellular matrix. Collagen V critically regulates fibrillogenesis and is expressed throughout tendon development and maturation. Clinically, deficiency of collagen V manifests as classic Ehlers-Danlos syndrome (cEDS), a disorder characterized by hyperextensible skin, joint hypermobility and instability, and impaired wound healing. Recent studies in mouse supraspinatus tendons-which experience complex, region-dependent loading environments at insertion and midsubstance-demonstrate that developmental collagen V deficiency results in altered tendon structure and biomechanical function. However, differences in structure, mechanics, and gene expression resulting from reduced collagen V expression from embryonic development versus reduction during homeostasis have not been clearly delineated in mature tendons. To address this gap, this study elucidated the role of collagen V on region-specific tendon structural, functional, and compositional properties in mature, day 150 supraspinatus tendons. Tendon-targeted Col5a1 deficiency from embryonic development resulted in substantial structural, mechanical, and transcriptional alterations, including disrupted fibril organization, compromised mechanical properties, and altered gene expression profiles. Conversely, acute deficiency and knockdown of Col5a1 in mature tendons resulted in relatively minimal changes. Collectively, these findings identify a distinct and critical role for collagen V during tendon development, rather than homeostasis, in establishing region-specific multiscale structural, mechanical, and molecular properties essential for mature supraspinatus tendon function.
    Keywords:  collagen V; structure‐function; supraspinatus tendon
    DOI:  https://doi.org/10.1002/jor.70164
  25. Semin Nephrol. 2026 Feb 24. pii: S0270-9295(26)00026-4. [Epub ahead of print] 151690
    The Role of the Epidermal Growth Factor Receptor in Kidney Tubulointerstitial Fibrosis.
    Raymond C Harris, Ming-Zhi Zhang.
      Kidney fibrosis is a common cause of chronic kidney disease. Experimental studies have demonstrated a role for the epidermal growth factor receptor (EGFR) signaling pathway in mediating the development and progression of kidney fibrosis. Deletion of Rhbdf2 (iRhom2), a member of the rhomboid family that regulates A disintegrin and metalloproteinase domain 17-mediated release of membrane-anchored proteins, including EGFR ligands, inhibited kidney interstitial fibrosis, which was accompanied by decreased EGFR activation in interstitial fibroblasts/myofibroblasts. In addition, overexpression of another EGFR ligand, heparin-binding epidermal growth factor-like growth factor, induced interstitial fibrosis in kidneys. Although EGFR activation did not induce myofibroblast transformation, it was necessary for the initial pericyte/fibroblast migration and proliferation prior to subsequent myofibroblast transformation by transforming growth factor beta or other profibrotic factors. Therefore, EGFR activation in kidney fibroblasts and pericytes serves as a specific initiator of interstitial fibrosis in response to kidney injury by stimulating pericyte/fibroblast migration and proliferation. These findings may also provide insight into the development of fibrosis in other organs and in other conditions.
    Keywords:  EGFR; HB-EGF; Myofibroblast; amphiregulin; pericyte
    DOI:  https://doi.org/10.1016/j.semnephrol.2026.151690
  26. Nanoscale Horiz. 2026 Feb 27.
    Nanoscale opportunities in extracellular matrix mimicry.
    L Andrew Lyon, Abbygail Caine, Elif Narbay, E Daniel Cárdenas-Vásquez.
      We present an overview of the composition, function, energetics, and dynamics of extracellular matrix and its relation to nanoscale structures and phenomena. These concepts are then related to the development of synthetic and biosynthetic materials that aim to mimic the extracellular matrix for regenerative medicine and tissue engineering technologies. Notable successes and advancements towards the goal of biomimicry are outlined, while remaining challenges and knowledge gaps towards that goal are highlighted. Finally, we frame the remaining challenges in the field in terms of nanoscience-related research opportunities that if solved, might prove to be transformative steps forward in the discipline.
    DOI:  https://doi.org/10.1039/d5nh00735f
  27. Front Cell Dev Biol. 2026 ;14 1757623
    A novel paradigm for chronic subdural hematoma: regenerative medicine strategies targeting the pathological microenvironment.
    Zhijian Xu, Song Yang, Guifang Zheng, Huahui Chen, Xing Wan, Hu Xu, Yutiao Xu, Jian Wang, Minfeng Tong, Qi Tu.
      This review systematically summarizes the pathological microenvironment characteristics of chronic subdural hematoma (CSDH) and the regenerative medicine strategies for its intervention. CSDH is no longer regarded as a simple mechanical hematoma but is recognized as a dynamic pathological process driven by chronic inflammation, abnormal angiogenesis, extracellular matrix (ECM) imbalance, and interactions among immune cells. The article focuses on key cellular and molecular mechanisms within the microenvironment and highlights regulatory strategies targeting inflammation, vascular leakage, and matrix remodeling. These strategies include immunomodulation, stem cell therapy, exosome- and nanomaterial-based delivery systems. Such innovative approaches aim to restore tissue homeostasis at the biological level, advancing CSDH treatment from traditional surgical drainage toward microenvironment remodeling and functional reconstruction. They provide a theoretical basis for achieving precise and regenerative clinical therapies.
    Keywords:  cSDH; microenvironment remodeling; pathological; regenerative medicine; targeted therapy
    DOI:  https://doi.org/10.3389/fcell.2026.1757623
  28. bioRxiv. 2026 Feb 09. pii: 2026.02.02.702917. [Epub ahead of print]
    Ctenophore mesoglea: building a mucus-like body.
    Sara Siwiecki, Ian M Black, Stephanie A Archer-Hartmann, Jiri Vlach, Casey Dunn, Parastoo Azadi, Alison Sweeney.
      Ctenophores are one of our most distant animal relatives and highly abundant and widespread marine predators, yet much of their biology remains undiscovered. Their bodies are dominated by a gelatinous, largely extracellular mesoglea of unknown composition. Ctenophores lack homologs for fibrous collagens that form the typical metazoan extracellular matrix (ECM), so the composition of their extracellular material is unknown. Using spectroscopic analyses of Mnemiopsis leidyi and Pleurobrachia pileus mesoglea, we found abundant mucus-related proteins and sulfated polysaccharides. The mucins and glycans appear unlinked, unlike the typical heavily glycosylated mucins. Our results suggest that ctenophores have a mucus-like mesoglea, a marked contrast from standard collagenous ECMs and mucus. This study indicates that ctenophores are even more different from other animals than previously appreciated, and expands our understanding of soft body composition and biophysics in animals.
    DOI:  https://doi.org/10.64898/2026.02.02.702917
  29. Curr Mol Med. 2026 Feb 20.
    Dynamic Changes of Extracellular Matrix in Sepsis: A Review.
    Mingjie Fu, Wenwei Xu, Jie Zhao, Shi Fu, Shuiqiao Fu, Liang Ma.
      During the pathogenesis of sepsis, extracellular matrix (ECM) impairment represents a critical pathological hallmark. The ECM not only plays pivotal roles in maintaining tissue architecture and physiological functions, but also actively participates in cellular signaling transduction and tissue repair mechanisms. Sepsisinduced systemic inflammatory responses and oxidative stress provoke ECM component degradation and structural remodeling, which, in turn, activate multiple intracellular and intercellular signaling cascades. Bioactive fragments derived from ECM degradation can function as signaling ligands that bind to specific cell surface receptors, triggering downstream pathways that regulate critical cellular processes, including survival, proliferation, migration, and inflammatory activation. The sustained activation of these signaling networks exerts profound pathophysiological consequences, potentially leading to vascular endothelial dysfunction, dysregulated immune cell hyperactivation, and coagulation system abnormalities. Furthermore, these signaling pathways mediate essential regulatory functions during the tissue remodeling phase in late-stage sepsis. While this dynamic ECM remodeling may facilitate tissue repair and regeneration, persistent dysregulation could result in maladaptive fibrosis and permanent organ dysfunction. Collectively, the ECM demonstrates multifaceted involvement in sepsis pathophysiology through its regulatory effects on cellular signaling, functional modulation, and tissue remodeling processes. This article systematically synthesizes current knowledge regarding ECM dynamics in sepsis pathogenesis.
    Keywords:  CD44; DDRs.; Integrins; collagens; elastin; proteoglycans
    DOI:  https://doi.org/10.2174/0115665240407854251202120058
  30. ACS Omega. 2026 Feb 17. 11(6): 9619-9629
    Study on the Antioxidant and Anti-Myocardial Fibrosis Effects of a Phenylpropanoid Compound (Xanthiumnolic C) Derived from Schisandra sphenanthera.
    Guannan Zhang, Ruixin Jing, Pilian Niu, Xinwei Shi, Mingsheng Bai.
      Myocardial fibrosis serves as a fundamental pathology for the pathogenesis and progression of cardiovascular diseases, characterized primarily by excessive proliferation of cardiac fibroblasts and pathological accumulation of extracellular matrix components. Although Schisandra sphenanthera fruit exhibits diverse pharmacological properties, its therapeutic potential for myocardial fibrosis remains unexplored. In this study, a phenylpropanoid compound designated W-23 (Xanthiumnolic C) was isolated from Schisandra sphenanthera. Structural elucidation was achieved through mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, and carbon spectrum analysis. The antioxidant and antimyocardial fibrosis activities of Xanthiumnolic C were evaluated in vitro. Xanthiumnolic C demonstrated significant antioxidant activity. In a cellular model of myocardial fibrosis, administration of Xanthiumnolic C significantly suppressed the expression of Vimentin (Vim), α-Smooth Muscle Actin (α-SMA), and proteins associated with the TGF-β/Smad signaling pathway, while concurrently downregulating levels of type I and III collagen. Furthermore, Xanthiumnolic C reduced the mRNA expression of Acta2, FN, Col 1 1a1, Vim, MMP-2, and MMP-9. Collectively, these effects ameliorated myocardial fibrosis, suggesting that Xanthiumnolic C holds promise as a potential therapeutic agent for antimyocardial fibrotic drug development.
    DOI:  https://doi.org/10.1021/acsomega.5c09835
  31. Pharmaceutics. 2026 Jan 28. pii: 172. [Epub ahead of print]18(2):
    Fibroblast-Targeted Nanodelivery Systems: Mechanisms of Collagen Remodeling Regulation and Novel Strategies for Scar Repair.
    Junshan Lan, Zhipeng Teng, Qian Huang, Fang Qin, Yibin Zheng, Yuting Liu, Yilin Chang, Xing Zhou, Xiaohui Li, Wenwu Wan, Lu Wang, Jie Lou.
      Scar formation is a common outcome of post-injury repair and can compromise both esthetic appearance and physiological function. Fibroblasts are central mediators of this process; their aberrant activation or differentiation into myofibroblasts drives fibrosis and excessive scar tissue accumulation. Nanodrug delivery systems (NDDSs) offer unique opportunities to modulate fibroblast behavior through cell-/microenvironment-guided targeting, controlled release, and stimuli-adaptive designs. Here, we summarize fibroblast biology across scar repair and delineate the mechanistic underpinnings of scar pathogenesis. We then synthesize recent progress in NDDS-enabled interventions for pathological scarring, with an emphasis on how materials design can be matched to fibroblast states and wound-stage cues. By connecting mechanisms to delivery strategies, this review provides a framework to guide the development of scar-minimizing therapies and functional tissue regeneration.
    Keywords:  fibroblasts; nanodrug delivery systems; scar formation; signal regulation
    DOI:  https://doi.org/10.3390/pharmaceutics18020172
  32. Arthritis Rheumatol. 2026 Feb 23.
    Long Non-Coding RNA H19 mediates STAT3 dependent activation of keratinocytes and fibroblasts in Systemic Sclerosis skin.
    Begoña Caballero-Ruiz, Christopher W Wasson, Rebecca L Ross, Francesco Del Galdo.
       OBJECTIVE: Dermal Systemic Sclerosis (SSc) fibroblasts and their exosomes can activate keratinocytes in SSc, with lncRNA H19 (H19) highlighted as the most upregulated RNA in their cargo compared to healthy control (HC). The role of H19 in SSc pathogenesis has never been investigated. Here we determine H19 role in the profibrotic activation of dermal fibroblasts and in their crosstalk with keratinocytes.
    METHODS: Skin biopsies were obtained from the forearms of patients with diffuse SSc (n=20) or HC (n=8) and dermal fibroblasts were explanted. In situ hybridization was used to determine H19 expression in the skin, paired with immunohistochemistry of STAT3 and Collagen1. H19 and STAT3 expression were modulated by retroviral transduction and siRNA. Gel contraction and transwell coculture were employed for functional studies.
    RESULTS: In SSc, high H19 expression in skin and explanted dermal fibroblasts compared to HC showed moderate correlation to well-described profibrotic markers. Knockdown of H19 in SSc fibroblasts decreased profibrotic gene expression and cell contraction ability. H19 overexpression was sufficient to induce a profibrotic phenotype in HC fibroblasts. Mechanistically, TGF-β, IL-6 and IL-11 significantly increased H19 expression in HC fibroblast (2.2, 1.4, 3.5-fold, respectively), through activation of STAT3. Additionally, the STAT3 and STAT1 activation of keratinocytes induced by coculture with SSc fibroblasts was suppressed by H19 knockdown.
    CONCLUSION: This study shows that lncRNA H19 is a key mediator of STAT3 induced changes in fibrotic activation of fibroblast and keratinocytes in SSc skin and could be considered a promising therapeutic target in tissue fibrosis.
    DOI:  https://doi.org/10.1002/art.70104
  33. Am J Respir Cell Mol Biol. 2026 Feb 11. pii: aanag022. [Epub ahead of print]
    RUNX1 is a mediator of fibrotic activation and epigenetic memory in lung fibroblasts.
    Rachel M Gilbert, Dakota L Jones, Jack Wellmerling, Nunzia Caporarello, Jeffrey A Meridew, Kyoung M Choi, Andrew J Haak, Patrick A Link, Qi Tan, Jeong-Heon Lee, Tamas Ordog, Giovanni Ligresti, Daniel J Tschumperlin.
      Repetitive injury is hypothesized to lead to progressive tissue fibrosis and end-stage organ failure. Whether tissue-resident mesenchymal cell populations retain epigenetic memory of prior injuries that contribute to this pathological process is unknown. Here we used a genetic lineage labeling approach to mark the lung mesenchyme prior to injury, then performed multi-modal analyses on isolated lung mesenchyme during the initiation, progression and resolution of the fibrotic response. Our results demonstrate the remarkable epigenetic and transcriptional plasticity of the lung mesenchyme during fibrotic activation and de-activation. Despite this plasticity, we also find that the lung mesenchyme exhibits an enhanced fibrotic program upon re-injury. We identify RUNX1 as a critical driver of both fibrotic activation and fibrotic memory. Comparison of fresh isolated and cultured lung mesenchyme demonstrates that RUNX1 is spontaneously activated in standard culture conditions, previously masking these roles of RUNX1. Targeted knockdown of RUNX1 dampens fibrotic mesenchymal cell activation immediately after cell isolation, but with reduced efficacy after only days of culture, confirming its functional importance to both early activation and long-term memory. Collectively, our findings implicate RUNX1 in the initiation and memory of fibrotic mesenchymal cell activation that together prime enhanced mesenchymal cell responses upon repeated injury.
    Keywords:  ATACseq; ChIPseq; Fibroblast activation; RNAseq; epigenetic; lung fibrosis; multi-omics
    DOI:  https://doi.org/10.1093/ajrcmb/aanag022
  34. Rev Med Virol. 2026 Mar;36(2): e70118
    Viral Pathogens and Pulmonary Fibrosis: EMT-Driven Mechanisms and Insights From Traditional Chinese Medicine.
    Ningzi Zang, Yingxu Wu, Pin Li, Yongming Liu, Shiwen Wang, Jiapeng Leng, Libin Zhan, Xiaodong Lyu, Lijian Pang, Jiaran Wang.
      Idiopathic pulmonary fibrosis (IPF) is a serious progressive complication of the respiratory system, which is profoundly associated with persistent extracellular matrix (ECM) deposition, fibrosis, and disrupted tissue regeneration. Emerging evidence shows that epithelial-mesenchymal transition (EMT) acts as a key factor in the pathogenesis of this idiopathic interstitial lung disease by connecting long-lasting epithelial damage to fibroblast accumulation and fibrotic processes. Viral pathogens, particularly emerging and re-emerging viruses, such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Influenza Virus, and Dengue Virus (DENV) and also those with oncogenic potential such as Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Hepatitis C Virus (HCV), have been demonstrated to be significantly associated with impaired epithelial signalling, persistent inflammation, and EMT induction. This underscores the presence of potential mechanistic overlap between viral infections and fibrotic complications of the respiratory system. On the other hand, investigations have also suggested the capacity of Traditional Chinese Medicine (TCM) agents to modulate various EMT-linked pathways, which are simultaneously involved in both viral infections and IPF development. These common signalling pathways include TGF-β, Wnt/β-catenin, PI3K/AKT, and NF-κB signalling, acting as potential therapeutic targets against fibrotic complications such as IPF. The present review aims to comprehensively describe current evidence on the dynamic cross-talk between viral pathogens, particularly SARS-CoV-2, Influenza Virus, and DENV, EMT, and lung fibrosis. Additionally, it critically discusses how TCM-derived bioactive agents can interfere with these interconnected processes. This review elucidates the mechanistic basis and therapeutic potential of TCM compounds in lung fibrosis, considering the wider context of virus-related EMT dysregulation.
    Keywords:  EMT; emerging viruses; idiopathic pulmonary fibrosis; traditional Chinese medicine (TCM)
    DOI:  https://doi.org/10.1002/rmv.70118
  35. Tissue Eng Part A. 2026 Feb 25. 19373341261424272
    A New Bioprinted Dual-Layered Corneal Structure Using Collagen-Based Bioinks.
    Huasheng Huang, Yunong Yuan, Yuan Fang, Chris Hodge, Constantinos Pestglou, Gordon G Wallace, Gerard Sutton, Jingjing You.
      Bioengineered corneal constructs are a promising solution to the global shortage of donor tissue. However, most current models lack anatomical curvature and appropriate extracellular matrix (ECM) composition of the native cornea, limiting their relevance for studying graft integration and stromal-endothelial interactions. In this study, we developed a bioprinted, dual-layer corneal model comprising corneal stromal cells laden in type I collagen (Col-I) and a monolayer of corneal endothelial cells supported by collagen type IV (Col-IV). The construct was printed onto a curved support to replicate the posterior curvature of the native cornea. The use of ECM-specific, human-derived collagen bioinks supported high cell viability (>90%) and the formation of a continuous endothelial layer. Histological and immunofluorescence analyses confirmed distinct layering and appropriate cellular morphology and phenotypic marker expression for both corneal stromal and endothelial cells. The construct retained its curvature, transparency, and interfacial integrity over 3 weeks in culture and demonstrated adherence when positioned over an ex vivo corneal tissue. This anatomically curved, multilayered in vitro model offers a physiologically relevant platform for exploring stromal-endothelial architecture and cell interaction in corneal tissue engineering applications.
    Keywords:  3D bioprinting; collagen; cornea; tissue engineering
    DOI:  https://doi.org/10.1177/19373341261424272
  36. Biogerontology. 2026 Feb 27. pii: 65. [Epub ahead of print]27(2):
    Adipocytes as core drivers of skin aging and novel targets for regeneration.
    Enhui Wang, Zijun Xu, Yuting Wang, Junbo Wang, Yanfei Jiang, Chunyue Zhao.
      Skin aging has traditionally been attributed to alterations in the epidermis and dermis, including keratinocyte senescence, extracellular matrix (ECM) degradation, and fibroblast dysfunction. In contrast, the role of skin-associated adipose tissue (SAAT), particularly dermal white adipose tissue (dWAT), has been largely overlooked and considered a passive structural filler. Emerging evidence indicates that adipocyte aging is not merely a consequence of skin aging but may serve as a critical upstream driver that shapes the local microenvironment. Age-related functional decline of adipocytes, including the senescence-associated secretory phenotype (SASP), metabolic reprogramming, and altered adipokine secretion, can promote dermal ECM deterioration, perturb fibroblast function, and promote chronic low-grade inflammation. Furthermore, regional heterogeneity of dWAT across anatomical sites contributes to the spatial variability of skin aging patterns, influencing both the timing and severity of structural changes. Mechanistically, an adipocyte-immune-fibroblast tri-cellular network integrates signals from senescent adipocytes, immune cells, and fibroblasts, thereby amplifying tissue-level aging phenotypes. Current anti-aging interventions, which largely target epidermal or dermal compartments or focus on restoring tissue volume, often fail to address adipocyte dysfunction and its downstream effects. Here, we propose a conceptual framework in which adipocyte aging functions as an initiating event in skin aging, and we discuss the potential of adipocyte-targeted strategies, including senolytics, senomorphics, and functional reprogramming, to restore skin homeostasis and delay aging. This adipocyte-centered perspective reframes the pathophysiology of skin aging and highlights novel therapeutic opportunities for regenerative dermatology.
    Keywords:  Adipocyte senescence; Adipocyte-targeted therapy; Dermal white adipose tissue; Fibroblast; Skin aging
    DOI:  https://doi.org/10.1007/s10522-026-10413-4
  37. Noncoding RNA. 2026 Feb 18. pii: 7. [Epub ahead of print]12(1):
    The Stiff Side of Cancer: How Matrix Mechanics Rewrites Non-Coding RNA Expression Programs.
    Alma D Campos-Parra, Jonathan Puente-Rivera, César López-Camarillo, Stephanie I Nuñez-Olvera, Nereyda Hernández Nava, Gabriela Alvarado Macias, Macrina Beatriz Silva-Cázares.
      Extracellular matrix (ECM) stiffening is a defining biophysical feature of solid tumors that reshape gene regulation through mechanotransduction. Increased collagen crosslinking and stromal remodeling enhance integrin engagement, focal-adhesion signaling and force transmission to the nucleus, where key hubs such as lysyl oxidase (LOX), focal adhesion kinase (FAK) and the Hippo co-activators YAP1 and TAZ (WWTR1) promote proliferation, invasion, stemness and therapy resistance. Here, we synthesize evidence that quantitative changes in matrix stiffness remodel the miRNome and lncRNome in both tumor and stromal compartments, including extracellular vesicle cargo that reprograms metastatic niches. To address heterogeneity in experimental support, we classify mechanosensitive ncRNAs into studies directly validated by stiffness manipulation (e.g., tunable hydrogels/AFM) versus indirect associations based on mechanosensitive signaling, and we summarize physiological versus pathophysiological stiffness ranges across tissues discussed. We further review competing endogenous RNA (ceRNA) networks converging on mechanotransduction nodes and ECM remodeling enzymes, and discuss translational opportunities and challenges, including targeting mechanosensitive ncRNAs, combining ncRNA modulation with anti-stiffening strategies, delivery barriers in dense tumors, and the potential of circulating/exosomal ncRNAs as biomarkers. Overall, integrating ECM mechanics with ncRNA regulatory circuits provides a framework to identify feed-forward loops sustaining aggressive phenotypes in rigid microenvironments and highlights priorities for validation in physiologically relevant models.
    Keywords:  cancer; lncRNAs; matrix stiffness; mechanotransduction; miRNAs
    DOI:  https://doi.org/10.3390/ncrna12010007
  38. J Nanobiotechnology. 2026 Feb 28.
    Targeted inhibition of RGS19 alleviates renal fibrosis by restoring autophagy and modulating immune cell infiltration.
    Xinhao Niu, Yufeng Zhao, Long Li, Xiaoqing Xu, Cuidi Xu, Jiaheng Wu, Xiaohan Yu, Yanbo Chen, Ruiming Rong, Bin Xu.
      Renal fibrosis, a progressive pathological feature of chronic kidney disease (CKD), is driven by impaired autophagic processes and persistent immune activation. The molecular mechanisms that interconnect these pathways remain inadequately understood. This study investigates the role of regulator of G-protein signaling 19 (RGS19), a novel autophagy-associated gene, in the pathogenesis of renal fibrosis. By analyzing transcriptomic data from the Gene Expression Omnibus (GEO) and applying machine learning algorithms, RGS19 was identified as a key fibrosis-related gene. In both in vitro and in vivo renal fibrosis models, we validated its functional role, focusing on autophagic flux and immune responses. We observed that RGS19 expression was elevated in fibrotic kidneys and correlated with increased CD8 + T cell infiltration. Knockdown of RGS19 using siRNA led to reduced p62 accumulation, suppressed rapamycin (p-mechanistic target of rapamycin (mTOR)) activity, and restored LC3B-II levels, reflecting enhanced autophagic flux. Additionally, the secretion of T cell chemoattractants, such as C-X-C motif chemokine ligand 9 (CXCL9) and C-X-C motif chemokine ligand 10 (CXCL10), was diminished. Notably, targeted delivery of RGS19 siRNA via RDYH58 nanoparticles effectively alleviated renal fibrosis in murine models by reducing collagen deposition and immune cell infiltration. These findings suggest that RGS19 plays a central role in linking autophagy dysfunction with immune activation in renal fibrosis and highlight its potential as a therapeutic target for CKD.
    Keywords:  Autophagy; Chronic kidney disease; Immune activation; Nanoparticle therapy; RGS19; Renal fibrosis
    DOI:  https://doi.org/10.1186/s12951-026-04098-7
  39. bioRxiv. 2026 Feb 22. pii: 2026.02.21.707196. [Epub ahead of print]
    Vascular Destabilization and Pericyte Detachment are Mediated by hIAPP Aggregation in Transgenic Mice.
    J Koepke, L Mateus Gonçalves, C Andrade Barboza, A C Aplin, D J Hackney, S A Gharib, O Mohn, M Teng, J J Castillo, J Almaça, R L Hull-Meichle.
       Aims/hypothesis: Human islet amyloid polypeptide (hIAPP) deposition is a common feature of type-2 diabetes (T2D). Previous studies have demonstrated hIAPP-mediated endothelial cell (EC) dysfunction and inflammation, but little is known about islet microvascular stability or pericyte function in hIAPP-containing islets. This study investigates how islet endothelial cells and pericytes are influenced by hIAPP aggregation.
    Methods: Bulk RNAseq and qPCR were conducted on hIAPP or vehicle treated MS-1 cells and bead-purified human islet CD31+ cells from donors with or without T2D to determine how islet ECs respond to hIAPP exposure. Confocal imaging of living pancreatic slices obtained from hIAPP transgenic mice was conducted to evaluate the effect of hIAPP deposition on islet pericyte function and vasomotor responses.
    Results: hIAPP-treated MS-1 cells and ECs purified from T2D islets demonstrate downregulation of leading-edge genes associated with extracellular matrix and cell adhesion pathways. Pericytes from hIAPP-expressing mouse islets appear detached from underlying endothelial cells, which was associated with impaired vasomotor responses to constrictive or dilatory stimuli.
    Conclusions/interpretation: hIAPP induces vascular destabilization by downregulating mRNA of key extracellular matrix and cell adhesion molecules in ECs, likely promoting the breakdown of EC-EC and EC-pericyte coupling. hIAPP disrupts EC-pericyte connections, and pericyte detachment ultimately impairs pericytes' ability to modulate capillary diameter without impairing intracellular Ca 2+ dynamics. Our data suggest that amyloid deposition compromises EC health and survival by altering islet microvascular morphology, stability, and function. This, in turn, may disrupt islet microvascular stability and exacerbate endocrine cell dysfunction in T2D.
    Research in context: What is already known about this subject?: - hIAPP is cytotoxic to islet endothelial cells and beta cells, and contributes to islet failure in type-2 diabetes (T2D)- hIAPP transgenic mice demonstrate islet capillary dilation, loss of vascular structures, and increased pericyte density- Impaired pericyte anchorage and vascular fragmentation drive diabetes-related vasculopathies in other tissues, like the retina, kidney, and brainWhat is the key question?: - How does the surviving microvasculature in islets respond to hIAPP deposition?What are the new findings?: - Endothelial cells demonstrate transcriptional downregulation of key genes involved in cytoskeleton, ECM, and cell-adhesion maintenance, including Thbs1 , Tln1 , and Plec . - Amyloid deposits disrupt homeostatic interactions between endothelial cells and pericytes.- Amyloid-adjacent islet pericytes are detached from endothelial cells and display impaired ability to modulate capillary diameter.How might this impact on clinical practice in the foreseeable future?: - Therapies targeting endothelial cell-pericyte interactions may restore islet microvascular stability and improve islet function, especially in the context of early T2D.
    DOI:  https://doi.org/10.64898/2026.02.21.707196
  40. Prog Mol Subcell Biol. 2026 ;63 47-82
    Collagen from Marine Sources for Potential Application in Wound Treatment.
    Eleonora Tassara, Marco Giovine, Marina Pozzolini.
      Collagen is a biocompatible, biodegradable, and low-immunogenic protein, making it an ideal candidate for regenerative medicine. Due to ethical/religious concerns and the risk of disease transmission from traditional terrestrial mammal sources (bovine/porcine), scientific interest has increasingly shifted toward the vast marine ecosystem as a sustainable and alternative source. This chapter explores the primary applications of marine-derived collagen in wound healing, detailing its unique biochemical and structural characteristics compared to terrestrial collagen. Collagen, a fibrous protein of the extracellular matrix (ECM), is defined by its triple-helix structure, stabilized by hydroxyproline. Marine collagen shows significant diversity between vertebrates (fish) and invertebrates (Porifera, Cnidaria, Mollusca, Annelida, Echinodermata). For instance, fish collagen, though abundant from fishing industry waste, often has lower thermal stability due to a reduced imino acid content. However, specific invertebrate collagens, such as those from sponges (Chondrosia reniformis) or mollusk byssal threads, exhibit unique mechanical properties and surprising thermal resistance. The chapter comprehensively reviews the latest innovative applications using marine collagen (from fish, jellyfish, sponges, and mollusks) or gelatin in scaffolds, films, and bioactive peptides to promote skin regeneration and wound repair. This highlights the vast, unexplored potential of marine biodiversity for developing more efficient and sustainable biomaterials.
    Keywords:  Biomaterials; Extracellular matrix (ECM); Marine biodiversity; Marine collagen; Regenerative medicine; Triple helix; Wound healing
    DOI:  https://doi.org/10.1007/978-3-032-17771-1_2
  41. FEBS J. 2026 Feb 22.
    Beyond the chaos: How architecture structures tumour biology.
    Lea Dörner, Catrin Lutz, Stefan Prekovic, Hendrik A Messal.
      Cancer is increasingly recognised as a complex and heterogeneous disease, shaped not only by genetic mutations but also by the physical and biochemical context in which tumours develop. The spatial position of a cell, including its physical, cellular and molecular surroundings, shapes its fate, phenotypic plasticity and potential to transform and drive tumour progression and evolution. Tissue architecture provides a powerful framework for understanding the complex dynamics of cancer. It integrates the structural organisation of the tumour and its surrounding tissue, the distribution of physical forces, biochemical niches, cellular neighbourhoods, and the broader tissue and organ context in which the tumour develops. Together, these elements form a dynamic and evolving landscape that is continuously remodelled through the multiscale communication of cellular, biochemical and mechanical components. Understanding the principles that govern these interactions reveals that cancer is not merely a chaotic aggregation of cells, but a patterned system shaped by coordinated spatial relationships. Here, we discuss the recent literature to examine how physical, biochemical and cellular relationships orchestrate tumour initiation, progression and treatment resistance, and how their collaboration acts not as a passive scaffold, but as the architect of tumour behaviour.
    Keywords:  Tissue architecture; biochemistry; biophysics; cellular neighbourhoods; microenvironment; tumour biology
    DOI:  https://doi.org/10.1111/febs.70470
  42. J Orthop Res. 2026 Mar;44(3): e70163
    Molecular Mechanisms of Rotator Cuff Degeneration Identified by Spatial Transcriptomics and Multiplex Immunofluorescence.
    Shiyi Yao, Renhao Yang, Shifeng Ling, Gen Li, Hanyu Wang, Renxuan Li, Yang Xu, Yin Zhang, Chengyu Zhuang, Lei Wang.
      Rotator cuff tear (RCT) is a prevalent age-related condition whose underlying mechanisms remain poorly understood. This study employed spatial transcriptomics and multiplex immunofluorescence (mIF) to investigate gene expression and spatial heterogeneity in rotator cuff tissues from elderly RCT patients compared to age-matched controls, aiming to uncover key molecular pathways. Tendon samples were collected from RCT patients (n = 10) and controls (n = 10). Five from each group underwent spatial transcriptomic sequencing for differential gene expression, functional enrichment, and cell interaction analyzes. Results were validated with mIF on the remaining samples. Compared to controls, the RCT group showed 1261 downregulated and 2789 upregulated genes. Spatial analysis revealed distinct expression gradients: COMP and CHI3L1 were upregulated in the bone region, CHI3L1 and MT1X in the mid-tendon, and MT1X and FMOD in the tendon area-confirmed by mIF. Biological processes also varied regionally: cartilage development and extracellular matrix (ECM) organization were enriched in the bone, while ECM and collagen fibril organization dominated mid-tendon and tendon regions. The PI3K-AKT and ECM-receptor interaction pathways were central to these processes. Tenogenic progenitor-like cells (TPLCs) were significantly reduced in RCT (p < 0.0001), whereas mesenchymal cells increased in bone and mid-tendon areas (p < 0.001, p < 0.01), consistent with structural gradients. These findings suggest that elderly RCT may arise from chronic inflammation, ECM dysregulation, and failed regeneration. Spatial transcriptomics identified repair-related genes (COMP, CHI3L1, MT1X, FMOD) with region-specific expression, providing new insights into pathology and potential therapeutic targets.
    Keywords:  multiplex immunofluorescence; rotator cuff tear; spatial transcriptomics
    DOI:  https://doi.org/10.1002/jor.70163
  43. Medicina (Kaunas). 2026 Feb 03. pii: 317. [Epub ahead of print]62(2):
    Nonlinear Microscopy of ECM Remodeling in Renal and Vascular Tissues: A Systematic Review Integrating Human AVF Imaging.
    Viltė Gabrielė Samsonė, Danielius Samsonas, Laurynas Rimševičius, Mykolas Mačiulis, Elena Osteikaitė, Birutė Vaišnytė, Edvardas Žurauskas, Virginijus Barzda, Marius Miglinas.
      Background and Objectives: Extracellular matrix (ECM) and collagen remodeling contribute to chronic kidney disease (CKD) progression and vascular access dysfunction. Conventional histological techniques rely on staining and provide limited sensitivity for detecting early or subtle ECM alterations. Nonlinear optical imaging modalities, including second-harmonic generation (SHG), third-harmonic generation (THG), and multiphoton fluorescence (MPF) microscopy, enable label-free, high-resolution visualization of fibrillar collagen and may offer additional structural information. This study aimed to evaluate the added value of nonlinear imaging beyond conventional histology for assessing ECM remodeling in renal and vascular tissues. Materials and Methods: A systematic literature review was conducted in accordance with the PRISMA 2020 guidelines. PubMed and Web of Science were searched for studies published between 1 January 2015, and 4 April 2025, investigating ECM or collagen remodeling in renal or vascular tissues using SHG, THG, or MPF microscopy. After screening 115 records, 10 studies were included in the qualitative synthesis. In addition, representative SHG, THG, and MPF images of excised human arteriovenous fistula (AVF) tissue were acquired as illustrative feasibility examples to demonstrate the application of these imaging modalities. The use of human tissue was approved by the Vilnius Regional Biomedical Research Ethics Committee (approval No. 2022/6-1443-917). Results: The included studies demonstrated that nonlinear microscopy enables label-free assessment of collagen density, organization, and fiber orientation. SHG imaging differentiated healthy from diseased tissues and has been reported to support fibrosis assessment and staging in preclinical and selected clinical studies and revealed microstructural remodeling patterns not readily detected by conventional histology. The illustrative AVF images demonstrated collagen disorganization consistent with patterns reported in the reviewed literature and are presented solely to demonstrate imaging feasibility, without implying disease phenotype or clinical outcome associations. Conclusions: Nonlinear optical microscopy provides complementary structural information on ECM organization that is not accessible with standard histological techniques. Further validation and methodological standardization are required to support its broader application in clinical nephrology and vascular medicine.
    Keywords:  arteriovenous fistula; collagen remodeling; extracellular matrix; fibrosis; nonlinear microscopy
    DOI:  https://doi.org/10.3390/medicina62020317
  44. Bone Res. 2026 Feb 25. pii: 27. [Epub ahead of print]14(1):
    TGF-β-induced fibrotic scar formation limits recovery of spinal cord injury.
    Dayu Pan, Panfeng Wu, Kathleen Noller, Patrick Cahan, Xu Cao.
      Spinal cord injury (SCI) often causes long-term disability. But effective means to promote proper regeneration after SCI has so far failed to reach the clinic. Here, we report that fibrotic scar formation at injury sites prevents recovery after SCI and that the inhibition of fibrotic scar formation significantly improved SCI recovery in adult mice. We found that after SCI there is an elevation of macrophages, which are a primary source of activated transforming growth factor-β 1 (TGF-β1) that in turn recruits mesenchymal stromal/stem cells (MSCs) to induce their fibroblast differentiation, thus promoting scar formation. We also found that activated TGF-β1 acts on resident pericytes in the endothelial niche of the blood-spinal cord barrier to promote their differentiation into fibroblasts, which also contributes to scarring. Interrupting these pathways by selective genetic KOs or treatment with a TGF-β-neutralizing antibody inhibited scar formation and improved SCI functional recovery. Notably, we found that neonatal mice recover scarlessly after SCI and with no active TGF-β at the injury site. Together, these findings suggest that fibrotic scarring occurs due to elevated activation of TGF-β, and preventing such activation or neutralizing active TGF-β may be an approach to improve outcome after SCI.
    DOI:  https://doi.org/10.1038/s41413-026-00507-7
  45. JBMR Plus. 2026 Mar;10(3): ziag018
    Ribosome heterogeneity and specialization in musculoskeletal physiology and pathology.
    Alzbeta Chabronova, Guus G H van den Akker, Tim J M Welting, Mandy J Peffers.
      Musculoskeletal (MSK) tissues are highly dynamic systems that rely on tightly regulated protein synthesis to maintain homeostasis and structural integrity, adapt to physiological stimuli, and respond to injury. The deregulation of protein synthesis is implicated in a wide range of MSK pathologies. At the core of protein synthesis are ribosomes, complex molecular nanomachines that translate mRNAs and generate proteins. Once considered uniform entities passively exerting their function, ribosomes are now recognized to be heterogeneous in their composition and capable of specialized functions. These emerging concepts of ribosome heterogeneity and specialization are increasingly recognized as key regulators of physiological and pathological cellular processes across fields. Although the MSK field has yet to fully embrace and integrate ribosome-centered research, accumulating evidence suggests that ribosome heterogeneity and specialization might have profound implications for MSK (patho)biology. In this review, we summarize the emerging data across MSK tissues (bone, skeletal muscle, articular cartilage, tendons, and ligaments), highlighting the roles of ribosomes in supporting development, maintaining homeostasis, and facilitating cellular and tissue functions and adaptations, but also driving pathological changes and disease progression. Furthermore, we also outline recent key technological and methodological advances that are critical for uncovering the full scope, significance, and dynamic regulation of ribosome heterogeneity and specialization in MSK (patho)biology. As the field moves forward, ribosome-centered research holds great promise in revealing new mechanisms underlying MSK biology and identifying novel therapeutic targets.
    Keywords:  2′-O-methylation; protein synthesis; pseudouridylation; ribosomal RNA; ribosomal proteins; ribosome heterogeneity; ribosome specialization; ribosome-associated proteins; snoRNAs; translation regulation
    DOI:  https://doi.org/10.1093/jbmrpl/ziag018
  46. Medicina (Kaunas). 2026 Jan 31. pii: 284. [Epub ahead of print]62(2):
    Tetranectin and Paraoxonase-1 as Markers of Heart Failure.
    Paula Alexandra Vulciu, Nicolae Catalin Valea, Dana Zdremtan, Chioreanu Alexandru, Norberth-Istvan Varga, Imola Donath-Miklos, Maria-Daniela Mot, Maria Puschita.
      Background and Objectives: This narrative review evaluates the potential of Tetranectin (TN) and Paraoxonase-1 (PON1) to bridge the gap between biological pathology and clinical risk stratification by mapping the "Fibrosis-Oxidative Axis". Materials and Methods: A targeted literature search was conducted using Scopus, PubMed, and Google Scholar to identify studies examining the diagnostic and prognostic value of TN and PON1 in heart failure (HF). Evidence was synthesized qualitatively to analyze their roles in structural fibrosis and oxidative defense. Results: Tetranectin functions as a structural indicator, where its dynamics reflect fibroblast activation, extracellular matrix (ECM) deposition, and protein sequestration during tissue remodeling. On the other hand, PON1 serves as a functional metabolic barometer; its reduced activity correlates with systemic oxidative burden, loss of endothelial protection, and pro-inflammatory signaling. These markers capture a bidirectional pathology where oxidative injury drives fibrotic remodeling, which subsequently continue metabolic dysfunction. A dual-biomarker profile is proposed to stratify disease activity: early-stage metabolic stress (reduced PON1) precedes structural changes, while progressive HF involves active fibrosis (altered TN) alongside persistent oxidative injury. Conclusions: The combined assessment of TN and PON1 offers a complementary approach to HF profiling, potentially refining risk stratification beyond hemodynamic parameters. However, clinical implementation requires large-scale validation to address standardization issues and specificity limitations regarding multimorbidity.
    Keywords:  biomarkers; extracellular matrix remodeling; fibrosis; heart failure; oxidative stress; paraoxonase-1; risk stratification; tetranectin
    DOI:  https://doi.org/10.3390/medicina62020284
  47. Eur J Ophthalmol. 2026 Feb 27. 11206721261427214
    Brain-derived neurotrophic factor in age-related macular degeneration.
    Haotian Liao.
      Age-related Macular Degeneration (AMD) is a leading cause of vision loss. There is no cure for AMD. Current treatments focus on preventing disease progression and preserving vision. In recent years, the role of brain-derived neurotrophic factor (BDNF) in AMD has attracted increasing attention. BDNF is widely involved in the physiology and pathophysiology of the retina. These include the development of photoreceptors during early development and synaptic communication between photoreceptors and retinal neurons. Under pathological conditions, BDNF affects the functions of multiple cell types in the retina including photoreceptors, ganglion cells, Müller cells, microglia cells, amacrine cells, and the retinal pigment epithelium (RPE). Importantly, BDNF does not act alone. Its function relates with other neurotrophic factors such as basic fibroblast growth factor (bFGF), ciliary neurotrophic factor (CNTF), and glial cell derived neurotrophic factor (GDNF). Meanwhile, the dynamic interaction between BDNF, its precursor protein proBDNF and the BDNF receptor TrkB not only affects the survival of retinal cells in AMD but may also guide the treatment strategy. Various approaches have been taken to deliver BDNF in animal models for managing AMD. Despite the exciting progress, challenges remain in implementing BDNF therapy as an effective treatment. In this review, we summarize the current research progress of BDNF in AMD and highlight the issues that need to be addressed before translation into clinical practice.
    Keywords:  AMD; BDNF; TrkB; retina
    DOI:  https://doi.org/10.1177/11206721261427214
  48. J Oral Biol Craniofac Res. 2026 Mar-Apr;16(2):16(2): 101420
    Effect of type I collagen on TLR-3 induced MMP-13 expression in human periodontal ligament fibroblasts.
    Ratthawut Namwad, Pitchaya Chaiyaraksa, Nirada Dhanesuan, Siriluck Tiranathanagul.
       Background: This study examined the effects of type I collagen, alone and in combination with poly I:C-a toll-like receptor 3 (TLR3) agonist-on matrix metalloproteinase-13 (MMP-13) expression and wound healing in human periodontal ligament (hPDL) fibroblasts.
    Methods: hPDL fibroblasts were cultured and divided into four treatment groups: control, type I collagen (50 μg/mL), poly I:C (10 μg/mL), and a combination of type I collagen with poly I:C. Cytotoxicity was evaluated using the MTT assay. Cell migration was assessed via scratch assay at 0, 24, and 48 h. MMP-13 expression was quantified at both the mRNA and protein levels by real-time PCR and ELISA, respectively.
    Results: After 24 h, the MTT assay indicated that none of the four treatment groups exhibited cytotoxicity toward hPDL fibroblasts. In the scratch assay at 24 and 48 h, type I collagen group demonstrated the fastest wound closure, whereas the poly I:C group showed the slowest migration. Regarding MMP-13 expression, the combination group displayed the highest mRNA levels, while ELISA revealed that both the combination and poly I:C groups had the greatest protein expression relative to the control.
    Conclusion: This study provides evidence for an interaction between extracellular matrix signals and innate immune activation. Type I collagen promoted hPDL fibroblast migration, whereas poly I:C-a TLR3 agonist-upregulated MMP-13 expression, with the greatest effect observed in combination with collagen.
    Keywords:  MMP-13; Periodontal ligament fibroblasts; TLR-3; Type I collagen; Wound healing
    DOI:  https://doi.org/10.1016/j.jobcr.2026.101420
  49. Cell Signal. 2026 Feb 24. pii: S0898-6568(26)00095-1. [Epub ahead of print] 112445
    FOXC2 regulates CYP1B1 transcription and activates the TGF-β/Smad pathway to promote pulmonary fibrosis.
    Wei Chen, Jie Peng, Xiangyi Tang, Yuting Xiao, Yi Chen, Liangjun Tang, Shao Ouyang.
      Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease, with unclear pathogenesis and limited therapeutic options. Here, we investigated the role and mechanism of forkhead box C2 (FOXC2) in pulmonary fibrosis. The results showed that FOXC2 expression was significantly upregulated in lung tissues of mice with bleomycin (BLM)-induced pulmonary fibrosis. In vitro experiments demonstrated that knockdown of FOXC2 inhibited transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in A549 alveolar epithelial cells, reduced cell migration and invasion, and suppressed the activation of the TGF-β/Smad signaling pathway. Mechanistically, FOXC2 could bind to the promoter of cytochrome P450 1B1 (CYP1B1) to regulate its transcriptional activation. Knockdown of CYP1B1 exerted similar inhibitory effects on EMT and the TGF-β/Smad pathway to FOXC2 knockdown, while overexpression of CYP1B1 reversed the inhibitory effect of FOXC2 knockdown on TGF-β1-induced EMT. In vivo experiments confirmed that downregulation of FOXC2 attenuated BLM-induced pulmonary fibrosis in mice, which was associated with reduced CYP1B1 expression and inhibited activation of the TGF-β/Smad pathway. Collectively, these findings suggest that FOXC2 promotes pulmonary fibrosis by regulating CYP1B1 transcription and activating the TGF-β/Smad pathway, providing a potential therapeutic target for pulmonary fibrosis.
    Keywords:  EMT; FOXC2; Pulmonary fibrosis; TGF-β/Smad signaling pathway
    DOI:  https://doi.org/10.1016/j.cellsig.2026.112445
  50. Mol Cell Biochem. 2026 Feb 23.
    Targeting EIF5A suppresses liver fibrosis through impairment of mitochondrial function in hepatic stellate cells.
    Yuzhu Di, Lubo Jin, Xiaoyu Zhang, Pengchao Deng, Feiyang Gao, Shizhu Jin.
      Liver fibrosis represents a significant clinical challenge. While targeting activated hepatic stellate cells (HSCs) is a promising therapeutic strategy, the specific role of Eukaryotic Translation Initiation Factor 5 A (EIF5A) in this process remains incompletely understood. EIF5A expression was analyzed in human fibrotic liver specimens and experimental mouse models. Its therapeutic potential was evaluated through pharmacological inhibition in fibrotic mice. Direct effects and mechanisms on HSCs were further investigated in vitro, with a focus on mitochondrial function. Immunostaining revealed a marked increase of EIF5A in activated HSCs from human fibrotic livers, which was consistent with findings in mice. Inhibition of EIF5A significantly attenuated liver fibrosis in vivo. Mechanistically, EIF5A deficiency directly impaired mitochondrial function in HSCs, leading to reduced ATP production, decreased mitochondrial membrane potential, and abnormal mitochondrial morphology, thereby suppressing their activation. Our results indicate that EIF5A contributes to HSC activation during liver fibrosis, in part through modulating mitochondrial bioenergetics. The concordant observations in human and mouse systems highlight the translational relevance of EIF5A, supporting its further investigation as a potential therapeutic target for liver fibrosis.
    Keywords:  EIF5A; Hepatic stellate cells; Liver fibrosis; Mitochondrial
    DOI:  https://doi.org/10.1007/s11010-026-05504-2
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