bims-supasi 2026-05-10 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2026–05–10
ten papers selected by
Jonathan Wolf Mueller, University of Birmingham

Arylsulfatase L is a Golgi chondroitin sulfatase regulating skeletal development.
Influence of Chondroitin Sulfate Concentration on the Physicochemical Properties of Acetaminophen-Releasing Cellulose/PVOH Membranes.
Chondroitin sulfate restores muscle mass via gut-muscle axis remodeling through sugar-bile acid metabolism reprogramming.
Expression of sulfate pathway genes in human neurodevelopment.
Squid cartilage-derived chondroitin sulfate from Uroteuthis chinensis: a novel marine prebiotic modulating gut microbiota and ameliorating ulcerative colitis.
Genetic Skeletal Disorders with Defects in Glycosaminoglycan Biosynthesis.
Free-standing chondroitin sulfate/collagen multilayered films as preliminary Bruch's membrane-mimetic platform for retinal pigment epithelial cell culture.
The Gut-Kidney-Metabolic Axis: Impact of Gut-Derived Uremic Toxins on Insulin Resistance in Diabetic Kidney Disease.
Gut-Derived Uremic Toxins as a Risk Factor for Vascular Damage in Patients with Chronic Kidney Disease.
DHEAS Elevation as the Early Biochemical Abnormality in ACTH-Secreting Pituitary Microadenomas in Children: Two Case Reports.

J Biol Chem. 2026 May 06. pii: S0021-9258(26)01983-6. [Epub ahead of print] 113111

Arylsulfatase L is a Golgi chondroitin sulfatase regulating skeletal development.

Marianna Maddaluno, Chiara De Leonibus, Eugenio Del Prete, Francesco Giuseppe Salierno, Daniela Intartaglia, Diego Carrella, Ivan Conte, Nicola Volpi, Carmine Settembre.

  Sulfatases are a family of enzymes that hydrolyze sulfate esters from various substrates. Defects, in sulfatase activity, are associated with various human diseases due to the accumulation of sulfated substrates. Deficiency in ARSL, a Golgi sulfatase, is associated with X-linked recessive chondrodysplasia punctata (CDPX), a disorder characterized by defects in cartilage and bone development. However, until now, ARSL function has remained unknown. In this study, we demonstrate that ARSL promotes 4-O-desulfation of Chondroitin Sulfate (CS) during proteoglycan biosynthesis. Chondrocytes lacking ARSL exhibit hypersulfated CS and altered responses to TGF-β stimulation. Loss of function of ARSL orthologous in medaka fish (Ol-Arsd) results in hyper-4-O-sulfated CS, skeletal malformations, and craniofacial defects that partly resemble the human CDPX phenotype. Our findings uncover a previously unrecognized step in glycosaminoglycan (GAG) maturation-Golgi-based desulfation-and reveal a new layer of regulatory control in skeletal development.

Keywords:  Chondroitin sulfate; Proteoglycan; Sulfatase; chondrodysplasia

DOI:  https://doi.org/10.1016/j.jbc.2026.113111
ACS Omega. 2026 Apr 28. 11(16): 24650-24664

Influence of Chondroitin Sulfate Concentration on the Physicochemical Properties of Acetaminophen-Releasing Cellulose/PVOH Membranes.

Juliano Brisola, Paula Paulino Silva, Francisnara Tonholi, Jéssica Bassetto Carra, Rúbia Casagrande, Paulo Rodrigo Stival Bittencourt, Gizilene Maria de Carvalho.

The integrity of the skin barrier is essential for protecting the body from external threats. However, mechanical trauma, thermal injuries, and chronic wounds can impair this barrier and increase susceptibility to secondary infections. Wound dressings capable of in situ drug release and skin regeneration have emerged as effective strategies to promote accelerated healing. Cellulose/poly-(vinyl alcohol) (Cel/PVOH) and cellulose/chondroitin sulfate (Cel/CS) membranes are particularly promising for this purpose. However, it is essential to understand how increasing the chondroitin sulfate content affects the physical and chemical properties of these membranes. In this study, Cel/PVOH membranes incorporated with acetaminophen were developed, with varying amounts of chondroitin sulfate. Structural characterization by FT-IR and XRD revealed that higher CS content reduced crystallinity, thermal stability, and water vapor permeability. SEM analysis showed increased surface porosity associated with CS incorporation. Membranes with higher CS levels exhibited enhanced fluid handling capacity (FHC), ranging from 3.48 to 5.15 g·10 cm-2·24 h-1. Drug release studies demonstrated a diffusion-controlled kinetic profile for acetaminophen. This work presents a simple method for fabricating membranes with desirable physicochemical and structural properties, highlighting their potential for use as bioactive dressings and transdermal drug delivery systems.

DOI: https://doi.org/10.1021/acsomega.6c01092
Imeta. 2026 Apr;5(2): e70118

Chondroitin sulfate restores muscle mass via gut-muscle axis remodeling through sugar-bile acid metabolism reprogramming.

Ruiyun Wu, Tao Wen, Nan Shang, Penghao Xie, Zhenyu Wang, Hang Li, Shaobo Li, Dequan Zhang.

  Glucocorticoid-induced myopathy is characterized by progressive muscle atrophy and impaired regeneration, yet effective microbiota-oriented interventions for preserving muscle homeostasis remain largely unexplored. Here, we demonstrate that dietary chondroitin sulfate (DCS) restores muscle mass and function through a microbiota-dependent gut-muscle metabolic axis. DCS failed to confer protection in germ-free or antibiotic-treated mice, establishing gut microbiota as a prerequisite for its efficacy. Microbiota transplantation and mono-colonization experiments identified Lactobacillus johnsonii Z-RW as a functionally relevant mediator capable of recapitulating muscle protection under controlled microbial conditions. Integrated metagenomic, metabolomic, and proteomic analyses revealed coordinated reprogramming of intestinal sugar utilization and bile acid metabolism following DCS administration. Notably, DCS promoted bile acid deconjugation and enrichment of secondary bile acids, coinciding with restoration of muscle regenerative and energetic programs, including upregulation of NMRK2, PAX7, and SIRT1. Metabolite supplementation further implicated bile acids as candidate mediators linking microbial metabolism to muscle phenotypes. To quantitatively integrate these shifts, we introduce the sugar-bile acid ratio as a systems-level descriptor of microbiota-driven metabolic remodeling. Our findings delineate a microbiota-dependent metabolic framework through which a functional polysaccharide reshapes intestinal biochemistry to influence distal muscle physiology. This work highlights bile acid-associated signaling as a central relay within the gut-muscle axis and provides a conceptual foundation for microbiota-targeted strategies to mitigate muscle wasting.

Keywords:  Lactobacillus johnsonii; NAD⁺ metabolism; chondroitin sulfate; glucocorticoid‐induced myopathy; gut–muscle axis; multi‐omics integration

DOI:  https://doi.org/10.1002/imt2.70118
J Neurogenet. 2026 May 08. 1-20

Expression of sulfate pathway genes in human neurodevelopment.

Prasidhee Vijayakumar, Kim M Summers, Paul A Dawson.

  Sulfate is a vital nutrient for healthy brain development. More than 90 sulfate-related genes are highly conserved across mammalian species, with 16 of these genes being clinically reportable for adverse brain conditions. To determine the potential involvement of additional sulfate-related genes in human neuropathology, this study curated the spatial and temporal expression patterns of all known sulfate biology genes in the human fetal brain from 8 to 37 post conception weeks (pcw) using data from the BrainSpan database and performed network analysis to cluster sulfate-related genes with genes involved in neurodevelopmental processes. A total of 64 sulfate-related genes were abundantly or moderately expressed in 11 brain regions throughout gestation. Steady state expression was observed for some of these genes from 8 to 37 pcw, including genes that encode sulfotransferases (CHST12, CHST7), sulfatases (ARSA, SULF2, TPST1, TPST2), sulfatase modifying enzyme (SUMF2), key enzymes in amino acid metabolism (CDO1, CTH), sulfate transporter (SLC26A11), as well as genes involved in neurodevelopmental processes (ACTG1, TUBA1A, MAPT, UBE3A, DCHS1, WWOX). Between 21-24 weeks, there were numerous clusters of sulfate biology genes with neurodevelopmental genes involved in neuronal migration (FAT4) and synaptogenesis (CBLN2, WNT4, MAPT, FOXP2). At 8-13 and 17-21 pcw, fifteen sulfate genes (ARSF, CHST1, CHST2, CHST13, GAL3ST3, GOT1, IDS, HS3ST2, HS3ST4, HS6ST3, SLC26A8, STS, SULT1A1, SULT4A1, UST) were expressed in the hippocampus and clustered with genes involved in neurogenesis, differentiation and synaptogenesis (MAPT, DNER, NEUROD1). Overall, this study identified 48 sulfate-related genes with moderate/abundant expression in the fetal brain that are coexpressed with genes for neurodevelopmental processes but are not considered in clinical settings. These findings provide information for future studies into the physiological roles of sulfate-related genes that are expressed in the fetal brain.

Keywords:  Brain development; genetics; neurodevelopment; sulfate; sulfation

DOI:  https://doi.org/10.1080/01677063.2026.2649162
Food Res Int. 2026 Jul 01. pii: S0963-9969(26)00818-5. [Epub ahead of print]235 119141

Squid cartilage-derived chondroitin sulfate from Uroteuthis chinensis: a novel marine prebiotic modulating gut microbiota and ameliorating ulcerative colitis.

Shiwei Chen, Hanjing Li, Rongkun Chen, Zihua Liang, Zongjie Ou, Pengzhe Zhang, Li Ni, Jiacong Deng, Xucong Lv.

  This study evaluated the prebiotic potential of chondroitin sulfate (CS) derived from the cartilage of the squid Uroteuthis chinensis, and its protective effects against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. Dietary intervention with squid-derived CS significantly attenuated characteristic UC symptoms, including body weight loss, colon shortening, and histopathological damage. Mechanistic analyses revealed that squid-derived CS exerted potent anti-inflammatory effects by downregulating key pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and alleviated oxidative stress by enhancing colonic antioxidant capacity, as evidenced by increased activities of catalase (CAT) and superoxide dismutase (SOD) and reduced myeloperoxidase (MPO) activity. Integrated 16S rRNA gene sequencing and metabolomics analyses demonstrated that squid-derived CS profoundly restructured gut microbial community composition by enriching putative beneficial bacteria (e.g., Bifidobacterium, Clostridium, Blautia) while reducing opportunistic pathogens (e.g., Enterococcus, Sutterellaceae, Clostridia_UCG-014). This favorable microbial shift was accompanied by a reconfiguration of the intestinal metabolome, characterized by elevated production of beneficial short-chain fatty acids (SCFAs) and decreased levels of pro-inflammatory metabolites such as tyramine. Furthermore, squid-derived CS effectively enhanced intestinal barrier integrity by upregulating key tight junction proteins (ZO-1, occludin, claudin-1), thereby preventing bacterial lipopolysaccharide (LPS) translocation and associated liver injury, as indicated by reduced serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Collectively, these findings demonstrate that dietary squid-derived CS protects against UC by modulating gut microbiota composition to enrich beneficial taxa, restoring microbial metabolite homeostasis, reinforcing the intestinal epithelial barrier, and suppressing inflammatory responses and oxidative stress. This study provides the first evidence that squid-derived CS acts as a novel and promising marine prebiotic candidate for gut health promotion, highlighting its potential as a sustainable functional ingredient derived from processing waste for gut-health-promoting foods.

Keywords:  Chondroitin sulfate; Functional food; Gut microbiota; Intestinal health; Prebiotic potential; Squid cartilage

DOI:  https://doi.org/10.1016/j.foodres.2026.119141
Mol Syndromol. 2026 Feb 26.

Genetic Skeletal Disorders with Defects in Glycosaminoglycan Biosynthesis.

Yuko Tsujioka, Pelin Ozlem Simsek Kiper, Sheila Unger, Atsuhiko Handa, Tatsuo Kono, Masahiro Jinzaki, Antonio Rossi, Andrea Superti-Furga, Gen Nishimura.

   Background: Proteoglycans are a major component of the connective tissue matrix, which consists of a core protein and covalently attached glycosaminoglycan (GAG) chains, which are highly sulfated polysaccharides with a tetrasaccharide linker for the core protein attachment. Impaired synthesis or degradation of GAG causes genetic disorders. In the 1950s, deficient lysosomal GAG degradation was discovered in mucopolysaccharidoses. In the 1990s, a defective enzyme for GAG synthesis was implicated in a variant of Ehlers-Danlos syndrome and an impaired GAG sulfation in diastrophic dysplasia. Newer studies have uncovered that abnormal GAG synthesis causes a large group of genetic skeletal disorders with joint and skin abnormalities.
Summary: The prototype of this group includes diastrophic dysplasia and Desbuquois dysplasia. The former is attributed to abnormal GAG sulfation, while the latter to impaired GAG chain elongation. Defective linker formation causes distinctive phenotypes termed linkeropathy. Moreover, there remain many disorders with defective GAG synthesis, in which the phenotypes are poorly documented and thus the clinical suspicion and even interpretation of molecular findings are challenging. Here, we attempt to review the skeletal manifestations of abnormal GAG synthesis disorders, based on our own experiences and previous reports. Each disorder has distinct clinical and radiological features, but they share some common skeletal manifestations, such as distal humeral hypoplasia, misshapen proximal femora, accelerated carpal ossification, and malsegmentation of the short tubular bones.
Key Message: Awareness of the phenotypic similarities and differences among this group of disorders facilitates our clinical and genetic practices for affected individuals.

Keywords:  Desbuquois dysplasia; Diastrophic dysplasia; Glycosaminoglycan; Linkeropathy; Proteoglycan; Skeletal dysplasia

DOI:  https://doi.org/10.1159/000551137
Int J Biol Macromol. 2026 May 02. pii: S0141-8130(26)02286-5. [Epub ahead of print]364 152359

Free-standing chondroitin sulfate/collagen multilayered films as preliminary Bruch's membrane-mimetic platform for retinal pigment epithelial cell culture.

Lan Duo, Pengfei Cheng, Wenpei Jiang, Quankui Lin.

  Age-related macular degeneration (AMD) is a leading cause of irreversible blindness, primarily associated with retinal pigment epithelial (RPE) cell degeneration. Although RPE cell therapy has emerged as a promising strategy for AMD, maintaining RPE cell attachment, organization, and functional characteristics remains a major challenge. In this study, free-standing chondroitin sulfate (CS)/collagen (Col) multilayered films were fabricated via spin-coating-assisted layer-by-layer (LbL) assembly and evaluated in vitro as preliminary Bruch's membrane (BM)-mimetic platform for supporting RPE growth and preserving cellular functionality. Genipin cross-linking improved the mechanical stability of the films and reduced their swelling behavior. ARPE-19 cells cultured on the 2 h cross-linked films showed improved attachment and proliferation compared with uncross-linked films, together with detectable RPE65 expression and several RPE-related functional features, including apical-basal differences in pigment epithelium-derived factor (PEDF) secretion, phagocytosis of labeled photoreceptor outer segments (POS), and formation of microvilli-like structures. Collectively, these findings suggest that CS/Col free-standing films can support ARPE-19 cell growth and maintain several RPE-related phenotypic and functional features in vitro, providing a preliminary BM-mimetic platform for future RPE culture studies.

Keywords:  Biomimetic scaffold; Free-standing film; Layer-by-layer

DOI:  https://doi.org/10.1016/j.ijbiomac.2026.152359
Int J Mol Sci. 2026 Apr 13. pii: 3472. [Epub ahead of print]27(8):

The Gut-Kidney-Metabolic Axis: Impact of Gut-Derived Uremic Toxins on Insulin Resistance in Diabetic Kidney Disease.

Charlotte Delrue, Margaux Vinckier, Reinhart Speeckaert, Stefania Marzocco, Marijn M Speeckaert.

  Chronic kidney disease (CKD), especially diabetic kidney disease (DKD), is characterized not only by progressive loss of renal function but also by profound metabolic disturbances, including insulin resistance (IR). Emerging evidence implicates gut-derived uremic toxins as mediators linking intestinal dysbiosis to metabolic and renal injury. Several microbial metabolites, for example, indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide, are known to accumulate in CKD due to decreased renal excretion and altered tubular secretion. In vitro and in vivo experiments indicate that these gut-derived nephrotoxins impair insulin signaling pathways in cells. This results in increased production of reactive oxygen species, activation of stress kinases, higher levels of inflammatory cytokines, and inhibitory serine phosphorylation of insulin receptor substrates. Consequently, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling is impaired, reducing cellular glucose uptake. At the same time, these toxins induce endothelial dysfunction and mitochondrial damage, not only causing systemic IR but also contributing to the progression of kidney disease. Observational data link higher plasma toxin levels with components of IR, rapid loss of renal function as measured by estimated glomerular filtration rate, and a high risk of cardiovascular events in CKD patients. Although causality in humans remains unproven, interventions targeting the microbiota, toxin binding, and oxidative stress pathways show promise. We propose an integrated gut-kidney-metabolic framework in which dysbiosis-driven toxin production may amplify IR and DKD progression.

Keywords:  chronic kidney disease; diabetic kidney disease; gut–kidney axis; indoxyl sulfate; insulin resistance; microbiota modulation; oxidative stress; p-cresyl sulfate; trimethylamine-N-oxide; uremic toxins

DOI:  https://doi.org/10.3390/ijms27083472
Int J Mol Sci. 2026 Apr 13. pii: 3487. [Epub ahead of print]27(8):

Gut-Derived Uremic Toxins as a Risk Factor for Vascular Damage in Patients with Chronic Kidney Disease.

María Carmen Ruiz Fuentes, Mahsa Rashki, Noelia Risquez Chica, Elena Clavero García, Elisa B Pereira Pérez, María José Espigares Huete, Rosemary Wangensteen.

  Patients with chronic kidney disease (CKD) have a markedly increased cardiovascular risk that is not fully explained by traditional risk factors. Gut-derived uremic toxins, indoxyl sulfate (IS), indole-3-acetic acid (IAA), and p-cresyl sulfate (pCS), are poorly cleared by dialysis and may contribute to vascular damage. This cross-sectional observational study included 70 patients with CKD under different clinical conditions (pre-dialysis, peritoneal dialysis, hemodialysis, and kidney transplantation) and 17 healthy controls. Serum levels of IS, IAA, pCS and Klotho were measured, and vascular damage was assessed by carotid intima-media thickness (IMT) using ultrasound. CKD patients showed higher concentrations of IS, IAA, and pCS compared with controls, with the highest levels observed in hemodialysis patients. Peritoneal dialysis was associated with elevated IS and pCS, whereas in kidney transplantation, IS and IAA levels did not differ significantly from controls, and pCS remained elevated. Carotid IMT was higher in patients with diabetes and those undergoing hemodialysis. IAA correlated significantly with left/mean IMT, and mean IMT was the only parameter associated with previous cardiovascular events. These findings suggest that gut-derived uremic toxins, particularly IAA, might be associated with subclinical vascular damage in advanced CKD, although larger studies are needed to confirm these associations.

Keywords:  cardiovascular disease; carotid intima media thickness; chronic kidney disease; dialysis; gut-derived uremic toxins; kidney transplantation

DOI:  https://doi.org/10.3390/ijms27083487
Endocr Metab Immune Disord Drug Targets. 2026 Apr 22.

DHEAS Elevation as the Early Biochemical Abnormality in ACTH-Secreting Pituitary Microadenomas in Children: Two Case Reports.

Qiting Zhang, Yiling Cui, Wenjun Long, Ling Hou, Yanqin Ying, Xiaoping Luo.

   INTRODUCTION: ACTH-secreting pituitary microadenomas are associated with insidious onset in children and atypical early clinical manifestations, making them highly susceptible to misdiagnosis and underdiagnosis. They are characterized by elevated ACTH and cortisol levels with a disrupted circadian rhythm. We reported two pediatric cases that showed significant elevation of Dehydroepiandrosterone Sulfate (DHEAS) and Androstenedione (Ad) in the early stage, while ACTH and cortisol were in the normal range or mildly abnormal.
CASE PRESENTATION: Case 1, a 13-year-old male, was admitted to the hospital with two years of growth retardation. The initial pituitary Magnetic Resonance Imaging (MRI) was normal. After one year, the patient developed Cushing's Syndrome (CS), and a repeat MRI suggested a pituitary microadenoma. Case 2, a 13.1-year-old female who had experienced excessive weight gain for two years and amenorrhea for 11 months. The child presented with CS initially, and the MRI revealed a pituitary microadenoma. Both of them were pathologically confirmed as ACTH-secreting pituitary microadenomas after Transsphenoidal Surgery (TSS).
CONCLUSION: This report demonstrates that in cases with a significant DHEAS elevation, even with near-normal ACTH/cortisol levels and negative pituitary MRI, high clinical suspicion for ACTH- secreting microadenomas should be maintained, warranting close follow-up and further evaluation.

Keywords:  ACTH; ACTH-secreting pituitary microadenomas; Cushing's disease; androstenedione; children; dehydroepiandrosterone sulfate

DOI:  https://doi.org/10.2174/0118715303421171260109070559