MicroRNA-221 Inhibits Latent TGF-β1 Activation through Targeting Thrombospondin-1 to Attenuate Kidney Failure-Induced Cardiac Fibrosis.

ABSTRACT: Kidney failure (KF) is associated with cardiac fibrosis and significantly increased mortality in heart failure. Thrombospondin-1 (TSP1), a key regulator of latent transforming growth factor-β1 (L-TGF-β1) activation, is a predicted target of miR-221. We hypothesized miR-221 attenuates severe KF-associated cardiac fibrosis via targeting of Thbs1 with subsequent inhibition of L-TGF-β1 activation. Rat cardiac fibroblasts (cFB) were isolated and transfected with microRNA-221 (miR-221) mimics or mimic control (miR-221 and MC) with or without exposure to L-TGF-β1. We demonstrate miR-221 downregulates Thbs1 via direct 3' untranslated region (3' UTR) targeting with consequent inhibition of L-TGF-β1 activation in cFB as proven by the significant reduction of myofibroblast activation, c

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC7645417 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature