Mechanisms of Epigenetic Regulation in the Fibrogenic Activation of Hepatic Stellate Cells in Non-alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is an extremely prevalent disease, and the presence and severity of liver fibrosis are considered one of the most important factors determining its prognosis. Hepatic stellate cells (HSCs) are essential in hepatic fibrogenesis associated with NAFLD. A number of factors underlying NAFLD pathogenesis may promote HSCs activation, leading to the development of profibrotic and proinflammatory signs. In addition, for the fibrogenic transdifferentiation of quiescent HSCs, alterations in multiple genes are necessary, where epigenetic regulation plays a defining role. Epigenetic regulation induces changes in gene activity without altering the coding sequence, and these changes are stably inherited after the factor causing the alteration has disappeared. Epigenetic modifications comprise several regulatory mechanisms, including DNA methylation, covalent histone modification, chromatin remodeling, and non-coding RNAs. Since the mechanisms underlying epigenetic regulation of HSCs fibrogenic activation are reversible and dynamic, molecular targeted therapies aimed at correcting these mechanisms provide promising prospects for novel therapeutic approaches for treating liver fibrosis