ArticleKidney international2017
Inhibition of TRPC6 channels ameliorates renal fibrosis and contributes to renal protection by soluble klotho.
Article in Kidney international, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 104 citations in OpenAlex.
- TRPC6 Inhibition Attenuates Renal Tubulointerstitial Fibrosis via the Reactive Oxygen Species/TXNIP/NLRP3 Signaling Pathway.Kidney & blood pressure research · 2026Article
- Perinephric fat volume and its negative correlation with the eGFR according to a population health screening: a cross-sectional study.Renal failure · 2025Article
- G protein-coupled receptor 107 deficiency promotes development of diabetic nephropathy.Molecular biomedicine · 2025Article
- TRPC3 contributes to cyclophosphamide-induced cystitis progression by enhancing bladder fibrosis through activation of the TGF-β/smad pathway.Frontiers in pharmacology · 2025Article
- The roles of TRPC6 in renal tubular disorders: a narrative review.Renal failure · 2024Review
- Clinical and pathological significance of Orai1 channel expression in human diabetic nephropathy.Kidney research and clinical practice · 2024Article
- Calcium signalling and transport in the kidney.Nature reviews. Nephrology · 2024Review
- Article
- TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway.Current medical science · 2024Article
- Roles of TRP and PIEZO receptors in autoimmune diseases.Expert reviews in molecular medicine · 2024Review
- [Platycodin D improves pulmonary fibrosis in mice by down-regulating TRPC6 expression and reducing ROS production in lung fibroblasts].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Deletion of TRPC6, an Autism Risk Gene, Induces Hyperexcitability in Cortical Neurons Derived from Human Pluripotent Stem Cells.Molecular neurobiology · 2023Article
- A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.International journal of molecular sciences · 2023Review
- TRPC expression in human periodontal ligament cells and the periodontal tissue of periodontitis mice: a preliminary study.Laboratory animal research · 2023Article
- An inactivating human TRPC6 channel mutation without focal segmental glomerulosclerosis.Cellular and molecular life sciences : CMLS · 2023Article
- Transient Receptor Potential Canonical 6 (TRPC6) Channel in the Pathogenesis of Diseases: A Jack of Many Trades.Inflammation · 2023Review
- Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury.International journal of molecular sciences · 2023Article
- Ion channels and channelopathies in glomeruli.Physiological reviews · 2023Review
- Klotho Protein Decreases MMP-Mediated Degradation of Contractile Proteins during Ischaemia/Reperfusion Injury to the Cardiomyocytes.International journal of molecular sciences · 2022Article
- The Effects of TRPC6 Knockout in Animal Models of Kidney Disease.Biomolecules · 2022Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 6 institutions in 3 countries.
Funding
Abstract
Fibrosis is an exaggerated form of tissue repair that occurs with serious damage or repetitive injury and ultimately leads to organ failure due to the excessive scarring. Increased calcium ion entry through the TRPC6 channel has been associated with the pathogenesis of heart and glomerular diseases, but its role in renal interstitial fibrosis is unknown. We studied this by deletion of Trpc6 in mice and found it decreased unilateral ureteral obstruction-induced interstitial fibrosis and blunted increased mRNA expression of fibrosis-related genes in the ureteral obstructed kidney relative to that in the kidney of wild-type mice. Administration of BTP2, a pyrazol derivative known to inhibit function of several TRPC channels, also ameliorated obstruction-induced renal fibrosis and gene expression in wild-type mice. BTP2 inhibited carbachol-activated TRPC3 and TRPC6 channel activities in HEK293 cells. Ureteral obstruction caused over a 10-fold increase in mRNA expression for TRPC3 as well as TRPC6 in the kidneys of obstructed relative to the sham-operated mice. The magnitude of protection against obstruction-induced fibrosis in Trpc3 and Trpc6 double knockout mice was not different from that in Trpc6 knockout mice. Klotho, a membrane and soluble protein predominantly produced in the kidney, is known to confer protection against renal fibrosis. Administration of soluble klotho significantly reduced obstruction-induced renal fibrosis in wild-type mice, but not in Trpc6 knockout mice, indicating that klotho and TRPC6 inhibition act in the same pathway to protect against obstruction-induced renal fibrosis. Thus klotho and TRPC6 may be pharmacologic targets for treating renal fibrosis.
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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.