A positive mechanobiological feedback loop controls bistable switching of cardiac fibroblast phenotype.

ABSTRACT: Cardiac fibrosis is associated with activation of cardiac fibroblasts (CFs), a pathological, phenotypic transition that is widely believed to be irreversible in the late stages of disease development. Sensing of a stiffened mechanical environment through regulation of integrin-based adhesion plaques and activation of the Piezo1 mechanosensitive ion channel is known to factor into this transition. Here, using integrated in vitro and in silico models, we discovered a mutually reinforcing, mechanical positive feedback loop between integrin β1 and Piezo1 activation that forms a bistable switch. The bistable switch is initiated by perturbations in matrix elastic modulus that amplify to trigger downstream signaling involving Ca²⁺ and YAP that, recursively, leads fibroblasts to further

SUBMITTER: Niu L 

PROVIDER: S-EPMC9448780 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature