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

Academic Article


  • The role of the transforming growth factor (TGF)-β pathway in myocardial fibrosis is well recognized. However, the precise role of this signaling axis in cardiomyocyte (CM) biology is not defined. In TGF-β signaling, SMAD4 acts as the central intracellular mediator. To investigate the role of TGF-β signaling in CM biology, the authors deleted SMAD4 in adult mouse CMs. We demonstrate that CM-SMAD4–dependent TGF-β 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-β pathway for the management of myocardial fibrosis.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Umbarkar P; Singh AP; Gupte M; Verma VK; Galindo CL; Guo Y; Zhang Q; McNamara JW; Force T; Lal H
  • Start Page

  • 41
  • End Page

  • 53
  • Volume

  • 4
  • Issue

  • 1