AMPK stimulation inhibits YAP/TAZ signaling to ameliorate hepatic fibrosis.

ABSTRACT: Hepatic fibrosis is driven by the activation of hepatic stellate cells (HSCs). The Hippo pathway and its effectors, YAP and TAZ, are key regulators of HSC activation and fibrosis. However, there is a lack of mechanistic understanding of YAP/TAZ regulation in HSCs. Here we show that AMPK activation leads to YAP/TAZ inhibition and HSC inactivation in vitro, while the expression of a kinase-inactive mutant reversed these effects compared to wild type AMPKɑ1. Notably, the depletion of LATS1/2, an upstream kinase of YAP/TAZ signaling, rescues YAP/TAZ activation, suggesting that AMPK may be mediating YAP/TAZ inhibition via LATS1/2. In the carbon tetrachloride mouse model of fibrosis, pharmacologic activation of AMPK in HSCs inhibits YAP/TAZ signaling and reduces fibrosis. The findings implicate

SUBMITTER: Shihan MH 

PROVIDER: S-EPMC10909858 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature