ArticleJournal of the American Society of Nephrology : JASN2014
Direct action of endothelin-1 on podocytes promotes diabetic glomerulosclerosis.
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. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Safety and efficacy of sparsentan versus irbesartan in focal segmental glomerulosclerosis and IgA nephropathy: a systematic review and meta-analysis of randomized controlled trials.BMC nephrology · 2024Pooled it
- Activation of the Endothelin System in Chronic Kidney Disease and Kidney Transplant Recipients-Implications for Disease Progression.International journal of molecular sciences · 2026Article
- Mechanisms of Podocyte Injury in Kidney Allografts.Kidney360 · 2026Review
- 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
- Cell-cell crosstalk in kidney health and disease.Nature reviews. Nephrology · 2026Review
- G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and Diabetes.Cells · 2025Review
- Endothelin receptor antagonists in chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Blood Pressure Management Strategies and Podocyte Health.American journal of hypertension · 2025Review
- Renal microcirculation and mechanisms in diabetic kidney disease.Frontiers in endocrinology · 2025Review
- Targeting endothelin signaling in podocyte injury and diabetic nephropathy-diabetic kidney disease.Journal of nephrology · 2025Review
- Specificity of endothelial cells in endothelial dysfunction of diabetic kidney disease and their crosstalk with neighboring cells: an updated review.Frontiers in endocrinology · 2025Review
- Podocyte-targeted therapies - progress and future directions.Nature reviews. Nephrology · 2024Review
- Mechanism of protective actions of sparsentan in the kidney: lessons from studies in models of chronic kidney disease.Clinical science (London, England : 1979) · 2024Review
- Sparsentan ameliorates glomerular hypercellularity and inflammatory-gene networks induced by IgA1-IgG immune complexes in a mouse model of IgA nephropathy.American journal of physiology. Renal physiology · 2024Article
- Crosstalk among podocytes, glomerular endothelial cells and mesangial cells in diabetic kidney disease: an updated review.Cell communication and signaling : CCS · 2024Review
- Cellular cross-talk drives mesenchymal transdifferentiation in diabetic kidney disease.Frontiers in medicine · 2024Review
- Crosstalk mechanisms between glomerular endothelial cells and podocytes in renal diseases and kidney transplantation.Kidney research and clinical practice · 2024Article
- Pathomechanisms of Diabetic Kidney Disease.Journal of clinical medicine · 2023Review
- Population pharmacokinetic analysis of sparsentan in healthy volunteers and patients with focal segmental glomerulosclerosis.CPT: pharmacometrics & systems pharmacology · 2023Article
- Molecular pathways that drive diabetic kidney disease.The Journal of clinical investigation · 2023Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endothelin system has emerged as a novel target for the treatment of diabetic nephropathy. Endothelin-1 promotes mesangial cell proliferation and sclerosis. However, no direct pathogenic effect of endothelin-1 on podocytes has been shown in vivo and endothelin-1 signaling in podocytes has not been investigated. This study investigated endothelin effects in podocytes during experimental diabetic nephropathy. Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs). We then generated mice with a podocyte-specific double deletion of ETAR and ETBR (NPHS2-Cre×Ednra(lox/lox)×Ednrb(lox/lox) [Pod-ETRKO]). In vitro, treatment with endothelin-1 increased total β-catenin and phospho-NF-κB expression in wild-type glomeruli, but this effect was attenuated in Pod-ETRKO glomeruli. After streptozotocin injection to induce diabetes, wild-type mice developed mild diabetic nephropathy with microalbuminuria, mesangial matrix expansion, glomerular basement membrane thickening, and podocyte loss, whereas Pod-ETRKO mice presented less albuminuria and were completely protected from glomerulosclerosis and podocyte loss, even when uninephrectomized. Moreover, glomeruli from normal and diabetic Pod-ETRKO mice expressed substantially less total β-catenin and phospho-NF-κB compared with glomeruli from counterpart wild-type mice. This evidence suggests that endothelin-1 drives development of glomerulosclerosis and podocyte loss through direct activation of endothelin receptors and NF-κB and β-catenin pathways in podocytes. Notably, both the expression and function of the ETBR subtype were found to be important. Furthermore, these results indicate that activation of the endothelin-1 pathways selectively in podocytes mediates pathophysiologic crosstalk that influences mesangial architecture and sclerosis.
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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.