ArticleThe Journal of clinical investigation2014
Endothelial mitochondrial oxidative stress determines podocyte depletion in segmental glomerulosclerosis.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
189 citing papers in PubMed, 1 synthesis or guideline pooled it, 283 citations in OpenAlex.
- Understanding AMD by analogy: systematic review of lipid-related common pathogenic mechanisms in AMD, AD, AS and GN.Lipids in health and disease · 2018Pooled it
- New therapeutic hope for rare podocytopathies.Pediatric nephrology (Berlin, Germany) · 2026Review
- Single-cell and high-resolution spatial profiling of podocytopathies reveals core mechanisms of podocyte injury.Science advances · 2026Article
- The Weary Gatekeeper: Podocyte Aging and Glomerular Decline.Journal of the American Society of Nephrology : JASN · 2026Article
- The endothelium response to kidney injury.Nature reviews. Nephrology · 2026Review
- Glomerulo-Tubular Crosstalk in Diabetic Kidney Disease: From Pathophysiology to Novel Therapeutics.Electrolyte & blood pressure : E & BP · 2026Review
- Hesperetin-7-O-Glucuronide Improves Endothelial Cell Function Through Improving NO/ET-1 Balance and Reducing Oxidative Stress via miRNAs.Current issues in molecular biology · 2026Article
- Podocyte-derived endothelin-1 and endothelial cell endothelin A receptors are essential for glomerular injury in mouse models of focal segmental glomerulosclerosis.Kidney international · 2026Article
- Endothelium-derived endothelin-1 mediates sickle cell nephropathy.Function (Oxford, England) · 2026Article
- Endothelial ferroptosis: a novel mechanism and therapeutic target in diabetic microvascular complications.Molecular medicine (Cambridge, Mass.) · 2026Review
- The glomerular endothelial glycocalyx as a therapeutic target in proteinuric kidney disease.Nature reviews. Nephrology · 2026Review
- Cell-cell crosstalk in kidney health and disease.Nature reviews. Nephrology · 2026Review
- Endothelial cell-released CD93 contributes to podocyte injury in idiopathic nephrotic syndrome.Science translational medicine · 2026Article
- Mitochondrial abnormalities in nondiabetic and nonhypertensive glomerular diseases: a comprehensive review.Molecular and cellular biochemistry · 2026Review
- cGAS-STING pathway in innate immunity and its cell-specific role in kidney diseases.Frontiers in immunology · 2026Review
- The role of endothelin receptor antagonists in kidney disease.Renal failure · 2025Review
- Mitochondrial dysfunction: the hidden catalyst in chronic kidney disease progression.Renal failure · 2025Review
- The albumin-to-creatinine ratio predicts and explores potential mediation of mortality in metabolic dysfunction-associated steatotic liver disease in U.S. adults: evidence from NHANES 1999-2018.BMC gastroenterology · 2025Article
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- The intelligent podocyte: sensing and responding to a complex microenvironment.Nature reviews. Nephrology · 2025Review
129 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Focal segmental glomerular sclerosis (FSGS) is a primary kidney disease that is commonly associated with proteinuria and progressive loss of glomerular function, leading to development of chronic kidney disease (CKD). FSGS is characterized by podocyte injury and depletion and collapse of glomerular capillary segments. Progression of FSGS is associated with TGF-β activation in podocytes; however, it is not clear how TGF-β signaling promotes disease. Here, we determined that podocyte-specific activation of TGF-β signaling in transgenic mice and BALB/c mice with Adriamycin-induced glomerulosclerosis is associated with endothelin-1 (EDN1) release by podocytes, which mediates mitochondrial oxidative stress and dysfunction in adjacent endothelial cells via paracrine EDN1 receptor type A (EDNRA) activation. Endothelial dysfunction promoted podocyte apoptosis, and inhibition of EDNRA or scavenging of mitochondrial-targeted ROS prevented podocyte loss, albuminuria, glomerulosclerosis, and renal failure. We confirmed reciprocal crosstalk between podocytes and endothelial cells in a coculture system. Biopsies from patients with FSGS exhibited increased mitochondrial DNA damage, consistent with EDNRA-mediated glomerular endothelial mitochondrial oxidative stress. Our studies indicate that segmental glomerulosclerosis develops as a result of podocyte-endothelial crosstalk mediated by EDN1/EDNRA-dependent mitochondrial dysfunction and suggest that targeting the reciprocal interaction between podocytes and endothelia may provide opportunities for therapeutic intervention in FSGS.
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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.