bims-migras 2026-04-05 papers

Issue of 2026–04–05
six papers selected by
Cliff Dominy

Int J Biol Macromol. 2026 Mar 30. pii: S0141-8130(26)01666-1. [Epub ahead of print] 151740

Tetraspanin 7-mediated endothelial migrasomes unveil a novel mechanism of angiogenesis through the PI3K/AKT pathway in diabetic wound healing.

Jie Wang, Miao Zhu, Zongzhe Jiang, Guohui Liao, Caimin Xu, Nan Jiang, Qi Chen.

BACKGROUND: Diabetic foot ulcer (DFU) is a complication of diabetes, characterized by impaired healing and chronic wounds that compromise quality of life. Migrasomes are newly discovered organelles involved in processes such as morphogenesis and angiogenesis, but their role in tissue repair and diabetic wound healing remains unknown. This study investigated the involvement of migrasomes in the pathogenesis and repair of DFU.
METHODS: Public DFU transcriptomic datasets from the Gene Expression Omnibus (GEO) were analyzed with DESeq2 to identify differentially expressed migrasome-related genes (DEMRGs). Machine-learning algorithms were applied to screen key DEMRGs and evaluate their associations with the immune microenvironment. Single-cell RNA sequencing (scRNA-seq) data were used to determine cell type-specific expression patterns. In addition, in vitro experiments were conducted to determine how the prioritized DEMRG regulates signaling pathways and modulates endothelial proliferation and migration. Finally, a diabetic murine wound model was established, and an endothelial-targeting adeno-associated virus (AAV) was used to overexpress the prioritized gene in vivo, followed by assessment of wound closure, histological repair, migrasome-associated membranous signals, and the activation of related signaling pathways.
RESULTS: RNA-sequencing analysis identified Tetraspanin 7 (TSPAN7) as a key DEMRG with strong diagnostic potential for DFU. scRNA-seq data demonstrated endothelial-specific downregulation of TSPAN7 in DFU lesions, which was confirmed by immunohistochemistry (IHC) and western blot in human DFU tissues. Wheat germ agglutinin (WGA) fluorescence staining showed that TSPAN7 overexpression increased migrasome formation in endothelial cells. Functionally, TSPAN7 overexpression promoted endothelial proliferation and migration, activated the PI3K/AKT signaling pathway, and upregulated vascular endothelial growth factor (VEGF). In diabetic mice, endothelial-specific Tspan7 overexpression consistently accelerated wound healing, improved re-epithelialization and collagen deposition, increased CD31 immunoreactivity, enhanced PIGK/TSPAN7 signals on WGA-labeled membranous structures, and restored PI3K/AKT phosphorylation in wound tissues.
CONCLUSION: In diabetic wounds, migrasome formation capacity is impaired. Restoring TSPAN7 expression activates PI3K/AKT signaling, thereby promoting angiogenesis and wound repair. TSPAN7-mediated migrasome formation represents a novel mechanism in DFU and a promising therapeutic target for enhancing healing in diabetic wounds.

Keywords: Diabetic foot ulcer; Machine learning; Migrasomes; PI3K/AKT pathway; Single cell; TSPAN7

DOI: https://doi.org/10.1016/j.ijbiomac.2026.151740

Nat Commun. 2026 Apr 02.

Migrasome-transported PTGES amplifies the PGE2 cascade in SPP1+ macrophages to drive oral leukoplakia carcinogenesis.

Ming-Jing Jiang, Hao-Yu Zhou, Yu-Ting Bai, Xiao-Jie Chen, Gang Zhou.

Oral leukoplakia (OLK) is a common oral potentially malignant disorder with a significant risk of transforming into oral squamous cell carcinoma (OSCC), yet the mechanisms remain poorly understood. Here we show that migrasomes, membranous organelles released by migrating cells, are detectable in epithelial cells of OLK and OSCC tissues and are more abundant in OSCC. Using carcinogenesis models, we transform human dysplastic oral keratinocyte (DOK) into oral carcinoma (DOK-TC) cells. Migrasomes derived from DOK-TC cells enhance interactions between DOK-TC cells and macrophages to promote carcinogenesis. Mechanistically, the uptake of prostaglandin E synthase (PTGES)-enriched migrasomes by macrophages increases PTGES expression and prostaglandin E2 secretion, which in turn induces an SPP1+ macrophage phenotype and promotes migration and proliferation. These findings uncover an unexplored migrasome-dependent immunomodulatory mechanism in OLK carcinogenesis and suggest migrasomal PTGES as a promising biomarker for early OSCC detection and a potential therapeutic target.

DOI: https://doi.org/10.1038/s41467-026-70824-2

J Proteome Res. 2026 Mar 30.

Proteome Profiling Reveals Inflammation and Fibrosis Biomarkers in Urinary Migrasomes of Patients with Diabetic Kidney Disease.

Xingyan Zhou, Ziwei Guo, Rui Zhang, Rui Yan.

Urinary extracellular vesicles are emerging markers reflecting the disease status of diabetic kidney disease (DKD), but their types and functions in DKD disease are not yet fully understood. This study applied Astral-DIA proteome for the in-depth profiling of urinary migrasomes (umig, a novel type of extracellular vesicles) and serum from DKD patients, aiming to identify protein biomarkers indicative of disease status. Proteome analysis revealed that protein-protein interactions were identified among LAMA1, ITGB3, FGG, and FGB in the differentially expressed proteins of serum and umig in the NC group and the DKD group. ITGB3 and FGB were closely related to inflammation and fibrosis pathways. The cellular source of umig may mainly come from podocytes, with some from monocytes/macrophages. NLRC4, ITGB3, and FGB were detected in umig. HK2 cells stimulated by DKD patient-derived umig showed increased expression of TLR4, p-NF-κB p65, NLRC4, caspase-1 p20, IL-1β, and TNF-α, suggesting that umig promotes inflammation through the TLR4-NF-κB pathway. In addition, inflammation and fibrosis occurred in the renal tissues of patients with DKD and db/db mice, accompanied by significantly elevated levels of NLRC4, ITGB3, and FGB. The abundance of NLRC4, ITGB3, and FGB in urinary migrasomes highlights the promise of migrasomes as noninvasive biomarkers for gauging inflammation and fibrosis status in DKD.

Keywords: diabetic kidney disease; fibrosis; inflammation; proteome; urinary migrasome

DOI: https://doi.org/10.1021/acs.jproteome.5c01073

Research (Wash D C). 2026 ;9 1220

A Native Bioactive Interface Functionalized with Osteoprogenitor Stem Cell-Derived Migrasomes for Enhanced Bone Regeneration.

Hongming Zhang, Jiajia Wang, Rong Yang, Xinyu Song, Rongpu Liu, Junyi Wang, Lingxi Meng, Zhuoran Xu, Ilya A Vinnikov, Guangzheng Yang, Wenjie Zhang.

The regeneration of large bone defects remains a major clinical challenge due to the lack of stable and effective osteoinductive signals. Although extracellular vesicles have shown promising potential for cell-free bone regeneration, their application is largely constrained by complex purification and embedding into scaffolds. Migrasomes, newly identified organelles with the extracellular matrix affinity, represent a promising yet underexplored avenue for cell-free tissue engineering. Here, we report a migrasome-enriched bioactive layer as a functional osteoinductive interface for cell-free bone regeneration. We demonstrated that osteoprogenitor stem cells (OPSCs) derived from human cortical bone exhibit robust osteogenic capacity and, upon osteogenic induction, promote the release and deposition of migrasomes together with calcium on culture surfaces. Utilizing these characteristics, we developed an in situ deposition strategy where OPSCs are preseeded on biphasic calcium phosphate (BCP) scaffolds, induced to mineralize, followed by decellularization. This process robustly preserves a native, osteogenic migrasome layer on the scaffold without the need for vesicle isolation or chemical conjugation. The resulting migrasome-functionalized scaffolds markedly up-regulated osteogenic gene expression and promoted bone regeneration in a murine calvarial defect model. Altogether, these findings validate migrasomes as a potent, endogenous signaling platform for bone tissue engineering. Moreover, our new paradigm for cell-free biomaterials employing cellular secretomes opens a new frontier in regenerative medicine, where the transient activity of cells is permanently captured to direct tissue repair.

DOI: https://doi.org/10.34133/research.1220

EBioMedicine. 2026 Apr 02. pii: S2352-3964(26)00119-2. [Epub ahead of print]127 106237

Migrasome-mediated clearance of excess PLK4 defines a targetable vulnerability.

Jihong Ma, Yuhan Guo, Yuening Jiang, Qilong Wang, Meiyu Bi, Tianzhen Wang, Yinan Xiao, Na Zhang, Pan Wang, Yu Wu, Bingteng Xie, Gang Wang, Mo Li.

BACKGROUND: Centrosome amplification caused by Polo-like kinase 4 (PLK4) overexpression promotes tumour initiation, yet sustained PLK4 accumulation is detrimental to cancer cell viability. While proteasomal degradation limits PLK4 levels, whether alternative clearance mechanisms exist remains unknown.
METHODS: We established inducible PLK4-overexpressing breast cancer cells and employed live-cell imaging, vesicular marker profiling, immunoprecipitation-mass spectrometry, and in vivo patient-derived xenograft models to investigate how cancer cells eliminate excess PLK4.
FINDINGS: In this study, we identified a previously unrecognised mechanism in which excess PLK4 is rapidly expelled via migrasomes. The tetraspanin protein TSPAN6 directly binds PLK4 with high affinity and mediates its incorporation into migrasomes for extracellular release. In breast cancer samples, PLK4 expression decreased while TSPAN6 increased during progression. TSPAN6 knockdown blocked PLK4 expulsion, leading to multipolar spindle formation, apoptosis, and suppression of tumour growth and metastasis in vivo.
INTERPRETATION: Migrasome-mediated clearance represents a non-proteasomal pathway maintaining centrosome homoeostasis in cancer cells. Targeting TSPAN6 to prevent PLK4 elimination selectively triggers mitotic catastrophe in PLK4-high tumours, highlighting a previously unrecognised therapeutic vulnerability.
FUNDING: This work was supported by the National Natural Science Foundation of China (NSFC) (T2225006, T2488301, and 82272948 to ML), Beijing Municipal Natural Science Foundation (Key program Z220011 to ML, 5254051 to TW), NSFC (82371640 to BX, 82403693 to PW), and the "Clinic + X" program of Peking University (to PW).

Keywords: Breast cancer; Centriole; Extracellular microenvironment; Migrasome; PLK4

DOI: https://doi.org/10.1016/j.ebiom.2026.106237