Micro RNAs in liver fibrosis: Focusing on the interaction with hedgehog signaling

Liver fibrosis is a repair process in response to damage in the liver; however, severe and chronic injury promotes the accumulation of fibrous matrix, destroying the normal functions and architecture of liver. Hepatic stellate cells(HSCs) are quiescent in normal livers, but in damaged livers, they transdifferentiate into myofibroblastic HSCs, which produce extracellular matrix proteins. Hedgehog(Hh) signaling orchestrates tissue reconstruction in damaged livers and contributes to liver fibrogenesis by regulating HSC activation. Micro RNAs(mi RNAs), endogenous small non-coding RNAs interfering with RNA post-transcriptionally, regulate various cellular processes in healthy organisms. The dysregulation of mi RNAs is closely associated with diseases, including liver diseases. Thus, mi RNAs are good targets in the diagnosis and treatment of various diseases, including liver fibrosis; however, the regulatory mechanisms of mi RNAs that interact with Hh signaling in liver fibrosis remain unclear. We review growing evidence showing the association of mi RNAs with Hh signaling. Recent studies suggest that Hh-regulating mi RNAs induce inactivation of HSCs, leading to decreased hepatic fibrosis. Although mi RNAdelivery systems and further knowledge of interacting mi RNAs with Hh signaling need to be improved for the clinical usage of mi RNAs, recent findings indicate that the mi RNAs regulating Hh signaling are promising therapeutic agents for treating liver fibrosis.