Mechanistic insights into post-translational modifications in hepatic fibrosis: pathogenic roles and therapeutic potentials.

Abstract

Hepatic fibrosis, a critical progression in liver disease, has been widely studied. While the activation of stellate cells and the accumulation of extracellular matrix components are recognized as key mechanisms, additional research is necessary to uncover further complexities. Recent investigations underscore the pivotal role of post-translational modifications (PTMs) in hepatic fibrosis. This study explores nine PTMs-methylation, acetylation, SUMOylation, Neddylation, phosphorylation, crotonylation, glycosylation, lactylation, and ubiquitination-each implicated in the pathogenesis of hepatic fibrosis. Furthermore, six classes of drugs-ACC inhibitors, ASK1 inhibitors, Akt activators, FXR agonists, PTP1B inhibitors, and HDAC inhibitors-are reviewed for their therapeutic potential in targeting PTMs to treat hepatic fibrosis.