ArticleJournal of the American Society of Nephrology : JASN2019
Glomerular Function and Structural Integrity Depend on Hyaluronan Synthesis by Glomerular Endothelium.
Article in Journal of the American Society of Nephrology : JASN, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45 citing papers in PubMed, 75 citations in OpenAlex.
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- The glomerular endothelial glycocalyx as a therapeutic target in proteinuric kidney disease.Nature reviews. Nephrology · 2026Review
- The Endothelial Glycocalyx: The First Line of Defense in the Prevention and Treatment of Kidney Diseases.Kidney medicine · 2025Review
- Metformin attenuates endoplasmic reticulum stress in diabetic kidney disease: mechanistic insights and future perspectives.International urology and nephrology · 2025Review
- Western diet-induced endothelial glycocalyx remodeling is partially reversed by fasting.American journal of physiology. Heart and circulatory physiology · 2025Article
- Time course and contributors to greater glycocalyx thickness and integrity following Western diet consumption.American journal of physiology. Heart and circulatory physiology · 2025Article
- Glycocalyx-targeted therapy prevents age-related muscle loss and declines in maximal exercise capacity.Aging · 2025Article
- What do You Need to Know after Diabetes and before Diabetic Retinopathy?Aging and disease · 2025Review
- The roles of hyaluronan in kidney development, physiology and disease.Nature reviews. Nephrology · 2024Review
- Therapeutic Targets for Diabetic Kidney Disease: Proteome-Wide Mendelian Randomization and Colocalization Analyses.Diabetes · 2024Article
- Role of endothelial hyaluronan in peritoneal membrane transport and disease conditions during peritoneal dialysis.Scientific reports · 2024Article
- Factors influencing glycocalyx degradation: a narrative review.Frontiers in immunology · 2024Review
- The complex pathology of diabetic nephropathy in humans.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Review
- Integrated multi-omics and bioinformatic methods to reveal the mechanisms of sinomenine against diabetic nephropathy.BMC complementary medicine and therapies · 2023Article
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- Early diabetic kidney disease: Focus on the glycocalyx.World journal of diabetes · 2023Review
- Endothelial glycocalyx in retina, hyperglycemia, and diabetic retinopathy.American journal of physiology. Cell physiology · 2023Review
- Phosphatidylinositol metabolism of the renal proximal tubule S3 segment is disturbed in response to diabetes.Scientific reports · 2023Article
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Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA glycocalyx envelope consisting of proteoglycans and adhering proteins covers endothelial cells, both the luminal and abluminal surface. We previously demonstrated that short-term loss of integrity of the luminal glycocalyx layer resulted in perturbed glomerular filtration barrier function.
methodsTo explore the role of the glycocalyx layer of the endothelial extracellular matrix in renal function, we generated mice with an endothelium-specific and inducible deletion of hyaluronan synthase 2 (Has2), the enzyme that produces hyaluronan, the main structural component of the endothelial glycocalyx layer. We also investigated the presence of endothelial hyaluronan in human kidney tissue from patients with varying degrees of diabetic nephropathy.
resultsEndothelial deletion of Has2 in adult mice led to substantial loss of the glycocalyx structure, and analysis of their kidneys and kidney function showed vascular destabilization, characterized by mesangiolysis, capillary ballooning, and albuminuria. This process develops over time into glomerular capillary rarefaction and glomerulosclerosis, recapitulating the phenotype of progressive human diabetic nephropathy. Using a hyaluronan-specific probe, we found loss of glomerular endothelial hyaluronan in association with lesion formation in tissue from patients with diabetic nephropathy. We also demonstrated that loss of hyaluronan, which harbors a specific binding site for angiopoietin and a key regulator of endothelial quiescence and maintenance of EC barrier function results in disturbed angiopoietin 1 Tie2.
conclusionsEndothelial loss of hyaluronan results in disturbed glomerular endothelial stabilization. Glomerular endothelial hyaluronan is a previously unrecognized key component of the extracelluar matrix that is required for glomerular structure and function and lost in diabetic nephropathy.
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