Trichostatin A inhibits the activation of Hepatic stellate cells by Increasing C/EBP-? Acetylation in vivo and in vitro.

ABSTRACT: Reversal of activated hepatic stellate cells (HSCs) to a quiescent state and apoptosis of activated HSCs are key elements in the reversion of hepatic fibrosis. CCAAT/enhancer binding protein ? (C/EBP-?) has been shown to inhibit HSC activation and promote its apoptosis. This study aims to investigate how C/EBP-? acetylation affects the fate of activated HSCs. Effects of a histone deacetylation inhibitor trichostatin A (TSA) on HSC activation were evaluated in a mouse model of liver fibrosis caused by carbon tetrachloride (CCl4) intoxication. TSA was found to ameliorate CCl4-induced hepatic fibrosis and improve liver function through increasing the protein level and enhancing C/EBP-? acetylation in the mouse liver. C/EBP-? acetylation was determined in HSC lines in the presence or absence of TSA, and the lysine residue K276 was identified as a main acetylation site in C/EBP-? protein. C/EBP-? acetylation increased its stability and protein level, and inhibited HSC activation. The present study demonstrated that C/EBP-? acetylation increases the protein level by inhibiting its ubiquitination-mediated degradation, and may be involved in the fate of activated HSCs. Use of TSA may confer an option in minimizing hepatic fibrosis by suppressing HSC activation, a key process in the initiation and progression of hepatic fibrosis.

SUBMITTER: Ding D 

PROVIDER: S-EPMC5849734 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature