TGFβ2 and TGFβ3 mediate appropriate context-dependent phenotype of rat valvular interstitial cells.

ABSTRACT: This study focused on characterizing the potential mechanism of valvular toxicity caused by TGFβ receptor inhibitors (TGFβRis) using rat valvular interstitial cells (VICs) to evaluate early biological responses to TGFβR inhibition. Three TGFβRis that achieved similar exposures in the rat were assessed. Two dual TGFβRI/-RII inhibitors caused valvulopathy, whereas a selective TGFβRI inhibitor did not, leading to a hypothesis that TGFβ receptor selectivity may influence the potency of valvular toxicity. The dual valvular toxic inhibitors had the most profound effect on altering VIC phenotype including altered morphology, migration, and extracellular matrix production. Reduction of TGFβ expression demonstrated that combined TGFβ2/β3 inhibition by small interfering RNA or neutralizing antibodie

SUBMITTER: Wang F 

PROVIDER: S-EPMC7900227 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature