ArticleThe Journal of biological chemistry2013
Transient receptor potential channel 6 (TRPC6) protects podocytes during complement-mediated glomerular disease.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- CaMKII phosphorylation promotes renal fibrosis in cisplatin induced chronic kidney disease via Smad 2/3 activation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Article
- Renin-angiotensin system-mediated nitric oxide signaling in podocytes.American journal of physiology. Renal physiology · 2024Article
- TRPC3 Is Downregulated in Primary Hyperparathyroidism.International journal of molecular sciences · 2024Article
- 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
- TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
- New insights into the immune functions of podocytes: the role of complement.Molecular and cellular pediatrics · 2023Review
- Role of ion channels in the mechanism of proteinuria (Review).Experimental and therapeutic medicine · 2023Review
- Ion channels and channelopathies in glomeruli.Physiological reviews · 2023Review
- CaMKIIβ knockdown decreases store-operated calcium entry in hippocampal dendritic spines.IBRO neuroscience reports · 2022Article
- Article
- Repurposing Riociguat to Target a Novel Paracrine Nitric Oxide-TRPC6 Pathway to Prevent Podocyte Injury.International journal of molecular sciences · 2021Article
- Role of actin cytoskeleton in podocytes.Pediatric nephrology (Berlin, Germany) · 2021Review
- Altered glycosylation of IgG4 promotes lectin complement pathway activation in anti-PLA2R1-associated membranous nephropathy.The Journal of clinical investigation · 2021Article
- Injured Podocytes Are Sensitized to Angiotensin II-Induced Calcium Signaling.Journal of the American Society of Nephrology : JASN · 2020Article
- TRPC Channels in Proteinuric Kidney Diseases.Cells · 2019Review
- Transmembrane insertases andThe Journal of biological chemistry · 2019Article
- Repression of hepatocyte nuclear factor 4 alpha by AP-1 underlies dyslipidemia associated with retinoic acid.Journal of lipid research · 2019Article
- Anti-PLA2R1 Antibodies Containing Sera Induce In Vitro Cytotoxicity Mediated by Complement Activation.Journal of immunology research · 2019Article
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Authors and funding
17 authors at 8 institutions in 4 countries.
Funding
Abstract
Gain-of-function mutations in the calcium channel TRPC6 lead to autosomal dominant focal segmental glomerulosclerosis and podocyte expression of TRPC6 is increased in some acquired human glomerular diseases, particularly in membranous nephropathy. These observations led to the hypothesis that TRPC6 overactivation is deleterious to podocytes through pathological calcium signaling, both in genetic and acquired diseases. Here, we show that the effects of TRPC6 on podocyte function are context-dependent. Overexpression of TRPC6 alone did not directly affect podocyte morphology and cytoskeletal structure. Unexpectedly, however, overexpression of TRPC6 protected podocytes from complement-mediated injury, whereas genetic or pharmacological TRPC6 inactivation increased podocyte susceptibility to complement. Mechanistically, this effect was mediated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activation. Podocyte-specific TRPC6 transgenic mice showed stronger CaMKII activation, reduced podocyte foot process effacement and reduced levels of proteinuria during nephrotoxic serum nephritis, whereas TRPC6 null mice exhibited reduced CaMKII activation and higher levels of proteinuria compared with wild type littermates. Human membranous nephropathy biopsy samples showed podocyte staining for active CaMKII, which correlated with the degree of TRPC6 expression. Together, these data suggest a dual and context dependent role of TRPC6 in podocytes where acute activation protects from complement-mediated damage, but chronic overactivation leads to focal segmental glomerulosclerosis.
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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.