Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2019; 25(31): 4468-4480
Published online Aug 21, 2019. doi: 10.3748/wjg.v25.i31.4468
MicroRNA-194 inactivates hepatic stellate cells and alleviates liver fibrosis by inhibiting AKT2
Jun-Cheng Wu, Rong Chen, Xin Luo, Zheng-Hong Li, Sheng-Zheng Luo, Ming-Yi Xu
Jun-Cheng Wu, Rong Chen, Xin Luo, Zheng-Hong Li, Sheng-Zheng Luo, Ming-Yi Xu, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Jun-Cheng Wu, Xin Luo, Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Author contributions: Xu MY designed the research; Wu JC and Chen R performed the research; Wu JC analyzed the data; Xu MY wrote the paper; Liu T and Luo X developed software necessary for performing the study.
Supported by the National Natural Science Foundation of China, No. 81600480, No. 81570547, and No. 81770597; and the Development Program of China during the 13th Five-year Plan Period, No. 2017ZX10203202003005.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Shanghai General Hospital (No. 2016KY025).
Conflict-of-interest statement: The authors declare that there are no conflicts of interest in this study.
ARRIVE guidelines statement: The manuscript was prepared and revised according to the ARRIVE guidelines.
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/
Corresponding author: Ming-Yi Xu, MD, PhD, Professor of Medicine, Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai 200080, China. xumingyi2014@163.com
Telephone: +86-21-63240090 Fax: +86-21-66283869
Received: March 29, 2019
Peer-review started: March 29, 2019
First decision: June 10, 2019
Revised: June 25, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: August 21, 2019
ARTICLE HIGHLIGHTS
Research background

Liver fibrosis is seriously endangering the safety of life. MiRNAs are reported as key regulators of cellular differentiation and of fibrosis-suppressive functions. Different classes of miRNAs have emerged as key regulators of important hepatic stellate cell (HSC) functions, such as activation, proliferation, and epigenetic gene regulation. Therefore, miRNAs represent novel mechanisms and targets for liver fibrosis. Loss of miR-194 has been reported in activated HSCs, but the actual role of miR-194 in liver fibrosis remains uncertain.

Research motivation

Our findings will provide a fundamental basis for the application of miR-194 in liver fibrosis therapy.

Research objectives

To measure the expression of miR-194 in fibrotic liver tissues and activated HSCs, and investigate biological functions and possible molecular mechanisms of miR-194 in liver fibrosis.

Research methods

We detected the expression of miR-194 in human fibrotic liver tissues, activated HSCs, and a CCl4 mouse model by qPCR. The biological behavior of miR-194 in vitro was then assessed by overexpression and knockdown of miR-194 in HSCs. In further molecular mechanism studies, we reintroduced miR-194 in mice using a miR-194 agomir to investigate the functions of miR-194 in liver fibrosis in vivo.

Research results

In the current study, we found that miR-194 was lacking in activated HSCs from both humans and mice. MiR-194 had a role of inhibiting the activation and proliferation of HSCs by suppressing AKT2. Meanwhile, we confirmed that reintroduction of miR-194 agomir through the tail vein could attenuate liver fibrosis in CCl4-treated mice in association with the reduction of AKT2. However, the specific regulatory role of miR-194 in liver fibrosis patients remains unclear, which needs to be validated in clinical studies.

Research conclusions

MiR-194 is downregulated in activated HSCs, which could inhibit the activation and proliferation of HSCs via suppressing AKT2. Reintroduction of miR-194 exerts a protective action against liver fibrosis.

Research perspectives

This study provides insight into the role of miR-194 in alleviating liver fibrosis by decreasing AKT2. Reintroduction of miR-194 might be a therapeutic approach to prevent and cure liver fibrosis.