ArticleJournal of the American Society of Nephrology : JASN2014
β-arrestin-1 drives endothelin-1-mediated podocyte activation and sustains renal injury.
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 43 papers.
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Who cites it
43 citing papers in PubMed, 80 citations in OpenAlex.
- DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS.Journal of the American Society of Nephrology : JASN · 2018Trial
- New therapeutic hope for rare podocytopathies.Pediatric nephrology (Berlin, Germany) · 2026Review
- The role of endothelin receptor antagonists in kidney disease.Renal failure · 2025Review
- Research trends and performance of endothelin A receptor antagonist in kidney care: a bibliometric analysis.Renal failure · 2025Article
- Selective endothelin A receptor antagonism in chronic kidney disease: improving clinical application.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Targeting endothelin signaling in podocyte injury and diabetic nephropathy-diabetic kidney disease.Journal of nephrology · 2025Review
- Renal microcirculation and mechanisms in diabetic kidney disease.Frontiers in endocrinology · 2025Review
- Comparing Long-Term Outcomes in Glomerular Disease Patients Presenting with Nephrotic Syndrome Versus Nephrotic Range Proteinuria.Life (Basel, Switzerland) · 2024Article
- β-Arrestin-2 enhances endoplasmic reticulum stress-induced glomerular endothelial cell injury by activating transcription factor 6 in diabetic nephropathy.World journal of diabetes · 2024Article
- Proteinuria and Progression of Renal Damage: The Main Pathogenetic Mechanisms and Pharmacological Approach.Medicina (Kaunas, Lithuania) · 2024Review
- Sparsentan is superior to losartan in the gddY mouse model of IgA nephropathy.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Mechanism of protective actions of sparsentan in the kidney: lessons from studies in models of chronic kidney disease.Clinical science (London, England : 1979) · 2024Review
- Targeting the Endothelin A Receptor in IgA Nephropathy.Kidney international reports · 2023Review
- Tenascin-C promotes the proliferation and fibrosis of mesangial cells in diabetic nephropathy through the β-catenin pathway.International urology and nephrology · 2023Review
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- Article
- Endothelial Endothelin Receptor A Expression Is Associated With Podocyte Injury and Oxidative Stress in Patients With Focal Segmental Glomerulosclerosis.Kidney international reports · 2021Article
- Endothelin-targeted new treatments for proteinuric and inflammatory glomerular diseases: focus on the added value to anti-renin-angiotensin system inhibition.Pediatric nephrology (Berlin, Germany) · 2021Review
- Nephrotoxicity of Anti-Angiogenic Therapies.Diagnostics (Basel, Switzerland) · 2021Review
- Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of endothelin-A receptor (ET(A)R) by endothelin-1 (ET-1) drives epithelial-to-mesenchymal transition in ovarian tumor cells through β-arrestin signaling. Here, we investigated whether this pathogenetic pathway could affect podocyte phenotype in proliferative glomerular disorders. In cultured mouse podocytes, ET-1 caused loss of the podocyte differentiation marker synaptopodin and acquisition of the mesenchymal marker α-smooth muscle actin. ET-1 promoted podocyte migration via ET(A)R activation and increased β-arrestin-1 expression. Activated ET(A)R recruited β-arrestin-1 to form a trimeric complex with Src leading to epithelial growth factor receptor (EGFR) transactivation and β-catenin phosphorylation, which promoted gene transcription of Snail. Increased Snail expression fostered ET-1-induced migration as confirmed by Snail knockdown experiments. Silencing of β-arrestin-1 prevented podocyte phenotypic changes and motility and inhibited ET(A)R-driven signaling. In vitro findings were confirmed in doxorubicin (Adriamycin)-induced nephropathy. Mice receiving Adriamycin developed renal injury with loss of podocytes and hyperplastic lesion formation; β-arrestin-1 expression increased in visceral podocytes and in podocytes entrapped in pseudo-crescents. Administration of the selective ET(A)R antagonist sitaxsentan prevented podocyte loss, formation of the hyperplastic lesions, and normalized expression of glomerular β-arrestin-1 and Snail. Increased β-arrestin-1 levels in podocytes retrieved from crescents of patients with proliferative glomerulopathies confirmed the translational relevance of these findings and suggest the therapeutic potential of ET(A)R antagonism for a group of diseases still needing a specific treatment.
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