ArticleThe Journal of clinical investigation2013
Inhibition of the TRPC5 ion channel protects the kidney filter.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 163 citations in OpenAlex.
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- Taming renal inflammation: signaling pathways and therapeutic advances in lupus nephritis.BMC nephrology · 2025Review
- Transient Receptor Potential Channels in Physiology and Pathophysiology: Special Issue.International journal of molecular sciences · 2025Article
- Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Adriamycin-induced podocyte injury via the Sema3A/TRPC5/Rac1 pathway.Frontiers in medicine · 2024Article
- Store-operated CaExperimental biology and medicine (Maywood, N.J.) · 2023Review
- Ion channels and channelopathies in glomeruli.Physiological reviews · 2023Review
- Role of ion channels in the mechanism of proteinuria (Review).Experimental and therapeutic medicine · 2023Review
- Article
- Transplanted organoids empower human preclinical assessment of drug candidate for the clinic.Science advances · 2022Article
- TRPC6 Inactivation Reduces Albuminuria Induced by Protein Overload in Sprague Dawley Rats.Cells · 2022Article
- Enhanced Orai1-mediated store-operated CaThe Journal of biological chemistry · 2022Article
- Mechanisms of podocyte injury and implications for diabetic nephropathy.Clinical science (London, England : 1979) · 2022Article
- Disease predictability review using common biomarkers appearing in diabetic nephropathy and neurodegeneration of experimental animals.Laboratory animal research · 2022Review
- Rho GTPases in kidney physiology and diseases.Small GTPases · 2022Article
- Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic Nephropathy.Journal of diabetes research · 2022Article
- Insulin-activated store-operated CaNature communications · 2021Article
- The glomerular filtration barrier: a structural target for novel kidney therapies.Nature reviews. Drug discovery · 2021Review
- Safety and Efficacy of GFB-887, a TRPC5 Channel Inhibitor, in Patients With Focal Segmental Glomerulosclerosis, Treatment-Resistant Minimal Change Disease, or Diabetic Nephropathy: TRACTION-2 Trial Design.Kidney international reports · 2021Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
An intact kidney filter is vital to retention of essential proteins in the blood and removal of waste from the body. Damage to the filtration barrier results in albumin loss in the urine, a hallmark of cardiovascular disease and kidney failure. Here we found that the ion channel TRPC5 mediates filtration barrier injury. Using Trpc5-KO mice, a small-molecule inhibitor of TRPC5, Ca2+ imaging in isolated kidney glomeruli, and live imagining of podocyte actin dynamics, we determined that loss of TRPC5 or its inhibition abrogates podocyte cytoskeletal remodeling. Inhibition or loss of TRPC5 prevented activation of the small GTP-binding protein Rac1 and stabilized synaptopodin. Importantly, genetic deletion or pharmacologic inhibition of TRPC5 protected mice from albuminuria. These data reveal that the Ca2+-permeable channel TRPC5 is an important determinant of albuminuria and identify TRPC5 inhibition as a therapeutic strategy for the prevention or treatment of proteinuric kidney disease.
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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.