Targeting YAP-mediated HSC death susceptibility and senescence for treatment of liver fibrosis.

ABSTRACT:

Background and aims

Liver fibrosis results from the accumulation of myofibroblasts (MFs) derived from quiescent HSCs, and yes-associated protein (YAP) controls this state transition. Although fibrosis is also influenced by HSC death and senescence, whether YAP regulates these processes and whether this could be leveraged to treat liver fibrosis are unknown.

Approach and results

YAP activity was manipulated in MF-HSCs to determine how YAP impacts susceptibility to pro-apoptotic senolytic agents or ferroptosis. Effects of senescence on YAP activity and susceptibility to apoptosis versus ferroptosis were also examined. CCl 4 -treated mice were treated with a ferroptosis inducer or pro-apoptotic senolytic to determine the effects on liver fibrosis. YAP was conditionally disrupte

SUBMITTER: Du K 

PROVIDER: S-EPMC10416614 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature