CDKN2a/p16 Antagonizes Hepatic Stellate Cell Activation and Liver Fibrosis by Modulating ROS Levels.

ABSTRACT: The lipid-storage hepatic stellate cells (HSC) play as pivotal role in liver fibrosis being able to trans-differentiate into myofibroblasts in response to various pro-fibrogenic stimuli. In the present study we investigated the role of CDKN2a/p16, a negative regulator of cell cycling, in HSC activation and the underlying mechanism. Levels of p16 were significantly down-regulated in activated HSCs isolated from mice induced to develop liver fibrosis compared to quiescent HSCs isolated from the control mice ex vivo. There was a similar decrease in p16 expression in cultured HSCs undergoing spontaneous activation or exposed to TGF-β treatment in vitro. More important, p16 down-regulation was observed to correlate with cirrhosis in humans. In a classic model of carbon tetrachloride (CCl4) indu

SUBMITTER: Lv F 

PROVIDER: S-EPMC7105638 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature