Cardiomyocyte SMAD4-Dependent TGF-? Signaling is Essential to Maintain Adult Heart Homeostasis.

ABSTRACT: The role of the transforming growth factor (TGF)-? pathway in myocardial fibrosis is well recognized. However, the precise role of this signaling axis in cardiomyocyte (CM) biology is not defined. In TGF-? signaling, SMAD4 acts as the central intracellular mediator. To investigate the role of TGF-? signaling in CM biology, the authors deleted SMAD4 in adult mouse CMs. We demonstrate that CM-SMAD4-dependent TGF-? signaling is critical for maintaining cardiac function, sarcomere kinetics, ion-channel gene expression, and cardiomyocyte survival. Thus, our findings raise a significant concern regarding the therapeutic approaches that rely on systemic inhibition of the TGF-? pathway for the management of myocardial fibrosis.

SUBMITTER: Umbarkar P 

PROVIDER: S-EPMC6390466 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature