MicroRNAs in liver fibrosis: Focusing on the interaction with hedgehog signaling

World J Gastroenterol. 2016 Aug 7;22(29):6652-62. doi: 10.3748/wjg.v22.i29.6652.

Abstract

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. MicroRNAs (miRNAs), endogenous small non-coding RNAs interfering with RNA post-transcriptionally, regulate various cellular processes in healthy organisms. The dysregulation of miRNAs is closely associated with diseases, including liver diseases. Thus, miRNAs are good targets in the diagnosis and treatment of various diseases, including liver fibrosis; however, the regulatory mechanisms of miRNAs that interact with Hh signaling in liver fibrosis remain unclear. We review growing evidence showing the association of miRNAs with Hh signaling. Recent studies suggest that Hh-regulating miRNAs induce inactivation of HSCs, leading to decreased hepatic fibrosis. Although miRNA-delivery systems and further knowledge of interacting miRNAs with Hh signaling need to be improved for the clinical usage of miRNAs, recent findings indicate that the miRNAs regulating Hh signaling are promising therapeutic agents for treating liver fibrosis.

Keywords: Hedgehog; Hepatic stellate cell; Liver fibrosis; MicroRNA.

Publication types

  • Review

MeSH terms

  • Animals
  • Hedgehog Proteins / physiology*
  • Hepatic Stellate Cells / physiology
  • Humans
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / therapy
  • MicroRNAs / physiology*
  • Signal Transduction / physiology*

Substances

  • Hedgehog Proteins
  • MicroRNAs