ArticleThe American journal of pathology2011
Angiotensin II contributes to podocyte injury by increasing TRPC6 expression via an NFAT-mediated positive feedback signaling pathway.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 208 citations in OpenAlex.
- The efficacy and safety of tacrolimus monotherapy in adult-onset nephrotic syndrome caused by idiopathic membranous nephropathy.Renal failure · 2017Trial
- Molecular mechanisms in podocytopathies: finding suitable targets for a new era of glomerular gene therapy.Clinical kidney journal · 2026Review
- Article
- Non-traditional cardiovascular risk factors after kidney transplantation.World journal of nephrology · 2025Review
- TRPC6 effects on albumin permeation, nephrin shedding, and apoptosis in podocytes: Role of calcineurin and metalloproteases.Physiological reports · 2025Article
- The CaPediatric nephrology (Berlin, Germany) · 2025Review
- Beyond Blood Pressure: Emerging Pathways and Precision Approaches in Hypertension-Induced Kidney Damage.International journal of molecular sciences · 2025Review
- Modulation of podocyte extracellular matrix remodeling in membranous nephropathy by the NFATc3/LRRC55/BK channel pathway.Journal of cell communication and signaling · 2025Article
- Effective calcineurin inhibitor treatment in adult-onset steroid-resistant nephrotic syndrome with a novel splice donor site variant of TRPC6: a case report.CEN case reports · 2025Article
- PIEZO1-Mediated Calcium Signaling and Podocyte Injury in Diabetic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2025Article
- Article
- Epigenetics of Hypertensive Nephropathy.Biomedicines · 2024Review
- Non-voltage-gated CaAmerican journal of physiology. Renal physiology · 2024Review
- Cytoskeleton Rearrangement in Podocytopathies: An Update.International journal of molecular sciences · 2024Review
- Vascular injury in glomerulopathies: the role of the endothelium.Frontiers in nephrology · 2024Review
- To Explore the Putative Molecular Targets of Diabetic Nephropathy and their Inhibition Utilizing Potential Phytocompounds.Current medicinal chemistry · 2024Review
- β-Arrestin pathway activation by selective ATR1 agonism promotes calcium influx in podocytes, leading to glomerular damage.Clinical science (London, England : 1979) · 2023Article
- A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.International journal of molecular sciences · 2023Review
- Expression profiles and potential roles of serum tRNA‑derived fragments in diabetic nephropathy.Experimental and therapeutic medicine · 2023Article
- Store-operated CaExperimental biology and medicine (Maywood, N.J.) · 2023Review
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
The transient receptor potential channel C6 (TRPC6) is a slit diaphragm-associated protein in podocytes involved in regulating glomerular filter function. Gain-of-function mutations in TRPC6 cause hereditary focal segmental glomerulosclerosis (FSGS), and several human acquired proteinuric diseases show increased glomerular TRPC6 expression. Angiotensin II (AngII) is a key contributor to glomerular disease and may regulate TRPC6 expression in nonrenal cells. We demonstrate that AngII regulates TRPC6 mRNA and protein levels in cultured podocytes and that AngII infusion enhances glomerular TRPC6 expression in vivo. In animal models for human FSGS (doxorubicin nephropathy) and increased renin-angiotensin system activity (Ren2 transgenic rats), glomerular TRPC6 expression was increased in an AngII-dependent manner. TRPC6 expression correlated with glomerular damage markers and glomerulosclerosis. We show that the regulation of TRPC6 expression by AngII and doxorubicin requires TRPC6-mediated Ca(2+) influx and the activation of the Ca(2+)-dependent protein phosphatase calcineurin and its substrate nuclear factor of activated T cells (NFAT). Accordingly, calcineurin inhibition by cyclosporine decreased TRPC6 expression and reduced proteinuria in doxorubicin nephropathy, whereas podocyte-specific inducible expression of a constitutively active NFAT mutant increased TRPC6 expression and induced severe proteinuria. Our findings demonstrate that the deleterious effects of AngII on podocytes and its pathogenic role in glomerular disease involve enhanced TRPC6 expression via a calcineurin/NFAT positive feedback signaling pathway.
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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.