ArticleJournal of the American Society of Nephrology : JASN2014
Syndecan-4 knockout leads to reduced extracellular transglutaminase-2 and protects against tubulointerstitial fibrosis.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03487861 (Development of a Diagnostic Kit for Urinary Transglutaminase 2 as a Biomarker for Kidney Allograft Fibrosis), which is not on this map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Development of a Diagnostic Kit for Urinary Transglutaminase 2 as a Biomarker for Kidney Allograft Fibrosis
Who cites it
48 citing papers in PubMed, 86 citations in OpenAlex.
- Natural killer cells in kidney immune surveillance, injury and fibrosis.Nature reviews. Nephrology · 2026Review
- Design of precision therapeutics for a CKD risk allele by targeting Shroom3-Rock interaction.Nature communications · 2025Article
- The Endothelial Glycocalyx: The First Line of Defense in the Prevention and Treatment of Kidney Diseases.Kidney medicine · 2025Review
- SDC4 drives fibrotic remodeling of the intervertebral disc under altered spinal loading.Cell death & disease · 2025Article
- D-glucuronyl C5-Epimerase Binds to EGFR to Suppress Kidney Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Critical Role for Transglutaminase 2 in Scleroderma Skin Fibrosis and in the Development of Dermal Sclerosis in a Mouse Model of Scleroderma.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Shed Syndecan-4 and Its Possible Roles in Osteoarthritis.Biomedicines · 2025Review
- Integrins in the kidney - beyond the matrix.Nature reviews. Nephrology · 2025Review
- Reduced glomerular and elevated tubulointerstitial transglutaminase pathway and its inhibition in a rat model of renal warm ischemia: implications for feline chronic kidney disease.Frontiers in veterinary science · 2025Article
- Shroom3-Rock interaction and profibrotic function: Resolving mechanism of an intronic CKD risk allele.bioRxiv : the preprint server for biology · 2024Article
- APP-CD74 axis mediates endothelial cell-macrophage communication to promote kidney injury and fibrosis.Frontiers in pharmacology · 2024Article
- Tissue transglutaminase exacerbates renal fibrosis via alternative activation of monocyte-derived macrophages.Cell death & disease · 2023Article
- Urinary complement proteins in IgA nephropathy progression from a relative quantitative proteomic analysis.PeerJ · 2023Article
- The fibrogenic niche in kidney fibrosis: components and mechanisms.Nature reviews. Nephrology · 2022Review
- Single-cell RNA sequencing data analysis suggests the cell-cell interaction patterns of the pituitary-kidney axis.Scientific reports · 2022Article
- Inhibiting Transglutaminase 2 Mediates Kidney Fibrosis via Anti-Apoptosis.Biomedicines · 2022Article
- Proteomic analysis reveals exercise training induced remodelling of hepatokine secretion and uncovers syndecan-4 as a regulator of hepatic lipid metabolism.Molecular metabolism · 2022Article
- Molecular profiling of urinary extracellular vesicles in chronic kidney disease and renal fibrosis.Frontiers in pharmacology · 2022Review
- Identification of Heparan Sulfate in Dilated Cardiomyopathy by Integrated Bioinformatics Analysis.Frontiers in cardiovascular medicine · 2022Article
- Development of a unilateral ureteral obstruction model in cynomolgus monkeys.Animal models and experimental medicine · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. The interaction of TG2 with the heparan sulfate proteoglycan syndecan-4 (Sdc4) regulates the cell surface trafficking, localization, and activity of TG2 in vitro but remains unstudied in vivo. We tested the hypothesis that Sdc4 is required for cell surface targeting of TG2 and the development of kidney fibrosis in CKD. Wild-type and Sdc4-null mice were subjected to unilateral ureteric obstruction and aristolochic acid nephropathy (AAN) as experimental models of kidney fibrosis. Analysis of renal scarring by Masson trichrome staining, kidney hydroxyproline levels, and collagen immunofluorescence demonstrated progressive fibrosis associated with increases in extracellular TG2 and TG activity in the tubulointerstitium in both models. Knockout of Sdc-4 reduced these effects and prevented AAN-induced increases in total and active TGF-β1. In wild-type mice subjected to AAN, extracellular TG2 colocalized with Sdc4 in the tubular interstitium and basement membrane, where TG2 also colocalized with heparan sulfate chains. Heparitinase I, which selectively cleaves heparan sulfate, completely abolished extracellular TG2 in normal and diseased kidney sections. In conclusion, the lack of Sdc4 heparan sulfate chains in the kidneys of Sdc4-null mice abrogates injury-induced externalization of TG2, thereby preventing profibrotic crosslinking of extracellular matrix and recruitment of large latent TGF-β1. This finding suggests that targeting the TG2-Sdc4 interaction may provide a specific interventional strategy for the treatment of CKD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.