bims-supasi 2026-07-05 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2026–07–05
six papers selected by
Jonathan Wolf Mueller, University of Birmingham

Expression and Spatial Localization of Glycosaminoglycan Types in Cartilage From Different Anatomical Locations.
Heparan Sulfate Proteoglycans in Immunity.
Evidence for Early Evolution of Sulfated Peptide Signaling in Plant Development.
Two distinct sulfated O-polysaccharides from the marine bacterium Vibrio sp. KMM 9700: Genomic prediction and structural elucidation.
Injectable chondroitin sulfate-glycosylated decellularized extracellular matrix microgels activate Wnt/β-Catenin signaling to promote functional muscle regeneration in VML.
Urinary indoxyl sulfate in children: age-related decline and its association with Bacteroidota in the gut microbiota.

J Histochem Cytochem. 2026 Jul 03. 221554261460112

Expression and Spatial Localization of Glycosaminoglycan Types in Cartilage From Different Anatomical Locations.

Manula S B Rathnayake, Reimer V Wolff, Nicole Kops, Karyna Kulakova, Gerjo J V M van Osch, Brooke Farrugia, Kathryn S Stok.

  Sulphated glycosaminoglycan (sGAG) is a major component of cartilage and known to be involved in cell signaling processes, but little is known about expression and localization in different cartilage types. Using common histochemical staining methods to assess regional sGAG distribution in bovine articular, meniscal, auricular, and nasal cartilage, different staining patterns were found for alcian blue, Safranin O and thionine. Immunohistochemistry to identify expression and location of different epitopes of chondroitin sulfate (C-0-S, C-4-S and C-6-S), dermatan sulfate, keratan sulfate, and heparan sulfate, also demonstrated regional differences which could not explain the differences in histochemical staining. Chondroitin sulfate and keratan sulfate were expressed in all cartilage types investigated, however keratan sulfate was not expressed in the superficial zone of articular cartilage. Dermatan sulfate was only present in tensile load-bearing zones of articular and meniscal cartilage, and in the perichondrium of auricular and nasal cartilage. Despite being hyaline, nasal cartilage and articular cartilage showed dissimilar sGAG expressions. In conclusion, sGAG localization in different types of cartilage is distinctly different, suggesting diverse structural and mechanical functions governed by GAGs. These differences are important for our understanding of the role of sGAG in cartilage function and in cartilage tissue engineering strategies.

Keywords:  articular; auricular; cartilage histochemistry; extracellular matrix; meniscal; nasal; proteoglycan; sulphated glycosaminoglycan

DOI:  https://doi.org/10.1369/00221554261460112
Proteoglycan Res. 2026 Apr;pii: e70048. [Epub ahead of print]4(2):

Heparan Sulfate Proteoglycans in Immunity.

Moe Iwai, Pyong Woo Park.

  In immune cells, heparin was first identified in mast cells in the 1940s, followed by the discovery of heparan sulfate in lymphocytes and granulocytes during the 1970s and 1980s. Subsequent decades of research have revealed how heparan sulfate and heparin, conjugated to core proteins as heparan sulfate proteoglycans (HSPGs), act as versatile modulators of immune function. It is now known that HSPGs are expressed by virtually all leukocytes and bind hundreds of immune mediators, including cytokines, proteases, growth factors, antimicrobial peptides, and extracellular matrix (ECM) components. HSPGs on leukocyte surfaces and within intracellular granules, as well as those on non-immune cells and within the ECM, shape immune cell development and responses to both endogenous and exogenous threats. Because immune activity must be tightly controlled to prevent collateral tissue damage, HSPGs play critical modulatory roles-facilitating, competing, protecting, presenting, or allosterically regulating immune factors. Consequently, mutations in HSPG core proteins and heparan sulfate biosynthetic enzymes, or dysregulation of HSPG-mediated immune interactions, contribute to diverse pathologies, including primary immunodeficiencies, autoimmune disease, infection, inflammatory tissue injury, allergy, and cancer. This review will highlight key mechanisms through which HSPGs regulate the development and function of major immune cell types.

Keywords:  adaptive immunity; glypicans; heparan sulfate; infectious disease; inflammatory disease; innate immunity; proteoglycan; serglycin; syndecans

DOI:  https://doi.org/10.1002/pgr2.70048
Plant Physiol. 2026 Jul 02. pii: kiag367. [Epub ahead of print]

Evidence for Early Evolution of Sulfated Peptide Signaling in Plant Development.

Devin V Tulio, Alexandra M Shigenaga, Shu-Zon Wu, Pamela C Ronald, Magdalena Bezanilla.

In plants, the cell wall fixes the position of each cell; therefore, during development, plants rely on cellular proliferation and expansion for tissue patterning and organ formation. How plant cells communicate with neighboring cells to coordinate expansion for properly patterned tissues and organs is not well understood. In seed plants, organ growth is known to be modulated by sulfotyrosyl peptide signaling. Here, we report that the activity of TYROSYL PROTEIN SULFOTRANSFERASE (TPST), which is responsible for the post-translational modification of sulfotyrosyl peptides, is essential for expansion during development in the non-vascular plant, Physcomitrium patens. Plants that harbor a null mutation in the gene encoding TPST (Δtpst) were smaller, formed fewer caulonemal filaments, and were unable to form expanded gametophores. In Δtpst multiple aspects of gametophore development were affected, including the first division of the gametophore initial, as well as reduced rates of cell division and expansion. Mutational analysis of P. patens TPST identified the residue Histidine 124, a candidate catalytic residue, as essential for TPST function. Notably, addition of the sulfated signaling peptide, PSY1 from either P. patens or Arabidopsis thaliana, rescued all Δtpst developmental deficits. Taken together, these data suggest that TPST functions to sulfate PSY, and this activity is necessary for plant growth and development. Furthermore, since addition of AtPSY fully rescues Δtpst and PpPSY promotes root elongation in Arabidopsis and rice, these findings suggest that PSY signaling is evolutionarily conserved.

DOI: https://doi.org/10.1093/plphys/kiag367
Carbohydr Res. 2026 Jul 02. pii: S0008-6215(26)00215-6. [Epub ahead of print]567 110026

Two distinct sulfated O-polysaccharides from the marine bacterium Vibrio sp. KMM 9700: Genomic prediction and structural elucidation.

Maxim S Kokoulin, Yulia V Savicheva, Ksenia V Isaeva, Lyudmila A Romanenko, Marina P Isaeva.

  Bacteria of the genus Vibrio dwelling in marine environment produce structurally diverse lipopolysaccharides (LPS) that play critical roles in environmental adaptation and host interactions. Here we report the complete structural elucidation of two O-polysaccharides (OPS) from the LPS of Vibrio sp. KMM 9700, isolated from the red alga Polysiphonia sp. Genomic analysis revealed an O-antigen gene cluster containing sulfotransferases (STs), glycosyltransferases (GTs), a PAPS biosynthesis operon, and the dTDP-Rha pathway. A GT and ST pair similar to that in the capsular polysaccharide cluster of V. chaetopteri KMM 8419T suggested the synthesis of a polysaccharide with α-l-rhamnopyranose (α-L-Rhap) 3-O-sulfate. An additional GT and ST pair in the cluster indicated the biosynthesis of another sulfated polysaccharide. Using chemical analyses, selective modifications, and NMR spectroscopy, we showed that both OPS coexist in the LPS preparation. The major OPS is a tetrasaccharide repeating unit with alternating 6-substituted α-D-Glcp and 2-substituted α-L-Rhap residues, featuring sulfate at O-3 and O-acetyl at O-4 of one α-L-Rhap residue. The minor OPS is a pentasaccharide repeating unit composed exclusively of α-L-Rhap residues with three 3-linked and two 2-linked residues, bearing sulfate groups at O-2 of two specific α-L-Rhap residues. Neither structure has been previously reported in bacterial glycans. The presence of two distinct sulfated OPS in a single Vibrio strain expands the known chemotypic diversity within the genus and suggests a sophisticated surface adaptation mechanism in marine environments.

Keywords:  Lipopolysaccharide; Marine bacteria; NMR; O-antigen gene cluster; O-polysaccharide; Sulfate; Vibrio

DOI:  https://doi.org/10.1016/j.carres.2026.110026
Bioact Mater. 2026 Nov;65 883-904

Injectable chondroitin sulfate-glycosylated decellularized extracellular matrix microgels activate Wnt/β-Catenin signaling to promote functional muscle regeneration in VML.

Siyu Liu, Sheng Ding, Shuwei Wang, Chunxiao Zhou, Xiang Liu, Hao Zhang, Long Yang, Zujian Feng, Deling Kong, Ningbei Yin, Weiwei Wang.

  Volumetric muscle loss (VML) overwhelms the endogenous regenerative capacity of skeletal muscle, leading to serious fibrosis, which further reduces muscle strength and severely affects patients' quality of life. While decellularized extracellular matrix (dECM) scaffolds offer tissue-specific biochemical cues for muscle regeneration, conventional decellularization protocols deplete critical glycosaminoglycans (GAGs), particularly chondroitin sulfate (CS), which are essential for growth factor sequestration and signaling pathway activation. Here, we developed injectable CS-glycosylated dECM microgels via microfluidic technology to restore GAG functionality to promote comprehensive muscle regeneration. We demonstrate that CS functionalization enhances myoblast adhesion, proliferation, migration, and differentiation in vitro. RNA sequencing analysis reveals that CS-mediated enhancement operates principally through activation of canonical Wnt/β-catenin signaling, with coordinated upregulation of downstream myogenic programs. In a rat tibialis anterior VML model, administration with high-CS formulations (H-CS@ECM) greatly promote muscle regeneration, function recovery and vascularization, with the muscle exhibiting enhanced-, blood perfusion, neuromuscular connectivity, and contractile protein expression at 8 weeks. Our findings suggest that CS-glycosylated dECM microgels possess significant translational potential as a minimally invasive and pro-regenerative implant material for VML repair. More broadly, this work establishes GAG modification as a generalizable design principle for enhancing dECM scaffold performance across diverse endogenous tissue regeneration applications, without the addition of exogenous growth factors, cytokines or drugs.

Keywords:  Chondroitin sulfate; Decellularized extracellular matrix; Injectable microgel; Muscle regeneration; Volumetric muscle loss

DOI:  https://doi.org/10.1016/j.bioactmat.2026.06.031
Biosci Microbiota Food Health. 2026 ;45(3): 197-203

Urinary indoxyl sulfate in children: age-related decline and its association with Bacteroidota in the gut microbiota.

Yuko Akagawa, Shohei Akagawa, Shoji Tsuji, Tomoki Kitawaki, Ayaka Ito, Mamoru Nakanishi, Takahiko Okada, Sohsaku Yamanouchi, Kazunari Kaneko.

  Urinary indoxyl sulfate (IS), a gut microbiota-derived uremic toxin, is associated with the adult gut microbiota and is elevated in children with autism spectrum disorder. However, its age-related trajectory and association with microbiota in healthy children remain uncharacterized. Therefore, we aimed to elucidate age-related changes in urinary IS in healthy children and to investigate the potential utility of urinary IS as a surrogate marker for their gut microbiota. We measured urinary IS/creatinine (Cr) ratios and analyzed the fecal gut microbiota composition (16S rRNA gene sequencing) in 102 healthy Japanese children aged 5 months to 12 years. Associations were assessed using Spearman's correlation. An empirical age-adjustment model (inverse proportional) was developed to derive an age-adjusted IS/Cr ratio (actual/predicted), thereby removing the strong age dependence before re-evaluating correlations with gut microbiota. The unadjusted IS/Cr ratio showed a strong negative correlation with age (rs=-0.47, p<0.001) and declined markedly during early childhood, stabilizing at approximately 5 years. Weak correlations with microbiota metrics were observed before adjustment; however, the age-adjusted IS/Cr ratio showed no correlation with age (rs=-0.03, p=0.768). Notably, age adjustment revealed significant positive correlations between the IS/Cr ratio and the phylum Bacteroidota (rs=0.26, p=0.008) and strengthened the correlation with the genus Bacteroides (rs=0.31, p=0.002), associations that were not apparent before adjustment. Correcting for this age-dependent variation is crucial, after which the IS/Cr ratio can serve as a potential non-invasive surrogate marker reflecting the abundance of Bacteroidota, particularly the genus Bacteroides, in the pediatric gut microbiota.

Keywords:  16S rRNA gene sequencing; Bacteroidota; gut microbiota; indoxyl sulfate; tryptophan

DOI:  https://doi.org/10.12938/bmfh.2025-107