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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2016; 22(29): 6652-6662
Published online Aug 7, 2016. doi: 10.3748/wjg.v22.i29.6652
MicroRNAs in liver fibrosis: Focusing on the interaction with hedgehog signaling
Jeongeun Hyun, Youngmi Jung
Jeongeun Hyun, Youngmi Jung, Department of Biological Sciences, College of Natural Science, Pusan National University, Pusan 46241, South Korea
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Supported by the National Research Foundation of Korea funded by the Korean Government (MEST) to Jung Y; No. 2013R1A2A2A01068268.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Youngmi Jung, PhD, Department of Biological Sciences, College of Natural Science, Pusan National University, Pusandaehak-ro 63beon-gil, Geumjeong-gu, Pusan 46241, South Korea. y.jung@pusan.ac.kr
Telephone: +82-51-5102262 Fax: +82-51-5812962
Received: April 1, 2016
Peer-review started: April 6, 2016
First decision: May 30, 2016
Revised: June 8, 2016
Accepted: June 29, 2016
Article in press: June 29, 2016
Published online: August 7, 2016
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: MicroRNA, Liver fibrosis, Hedgehog, Hepatic stellate cell

Core tip: MicroRNAs (miRNAs) influence various biological responses by controlling gene expression. Recent studies investigate the roles of miRNAs in liver fibrosis, due to their potential as biomarkers and therapeutic agents. Hedgehog (Hh) signaling contributes to hepatic fibrosis. Hence, regulation of Hh signaling is one of the therapeutic strategies against liver fibrogenesis. Therefore, we introduce miRNAs relevant to Hh signaling and discuss the interaction of miRNAs with Hh signaling, with a particular focus on the anti-fibrotic effect of Hh-regulating miRNAs in liver diseases. This review suggests that miRNAs-mediating Hh signaling are the novel diagnostic and therapeutic targets for treating liver disease.