Inhibition of TRPC6 channels ameliorates renal fibrosis and contributes to renal protection by soluble klotho.

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 express

SUBMITTER: Wu YL 

PROVIDER: S-EPMC5357448 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature