Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2021; 27(14): 1419-1434
Published online Apr 14, 2021. doi: 10.3748/wjg.v27.i14.1419
Lipotoxic hepatocyte-derived exosomal miR-1297 promotes hepatic stellate cell activation through the PTEN signaling pathway in metabolic-associated fatty liver disease
Xin Luo, Sheng-Zheng Luo, Zi-Xin Xu, Cui Zhou, Zheng-Hong Li, Xiao-Yan Zhou, Ming-Yi Xu
Xin Luo, Sheng-Zheng Luo, Zi-Xin Xu, Cui Zhou, Zheng-Hong Li, Xiao-Yan Zhou, Ming-Yi Xu, Department of Gastroenterology, Shanghai General Hospital, Shanghai 200080, China
Author contributions: Xu MY designed the research; Luo X and Luo SZ performed the research; Xu ZX and Li ZH analyzed the data; Luo X wrote the paper; Zhou C and Zhou XY developed software necessary for performing the study.
Supported by The National Natural Science Foundation of China (General Program), No. 81770597; and the Development Program of China during the 13th Five-year Plan Period, No. 2017ZX10203202003005.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Shanghai General Hospital.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals and approved by the Ethical Committee of the Shanghai General Hospital.
Conflict-of-interest statement: The authors hereby declare that no conflict of interest exists.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Ming-Yi Xu, MD, Chief Doctor, Professor, Department of Gastroenterology, Shanghai General Hospital, No. 100 Haining Road, Shanghai 200080, China.
Received: October 10, 2020
Peer-review started: October 10, 2020
First decision: January 23, 2021
Revised: February 5, 2021
Accepted: March 7, 2021
Article in press: March 7, 2021
Published online: April 14, 2021
Research background

Accumulating evidence has revealed that exosomes play an important role in the progression of metabolic-associated fatty liver disease, but the exact mechanism remains unclear.

Research motivation

Previous studies demonstrated that exosomes from lipotoxic hepatic cells could contribute to hepatic stellate cell (HSC) activation, but the specific cellular crosstalk interaction was not fully illustrated. We aimed to figure out if exosomal microRNA could participate in this procedure.

Research objectives

To determine the role of exosomal miR-1297 in the metabolic-associated fatty liver disease cell model.

Research methods

miRNA sequencing was conducted to screen differentially-expressed microRNAs. In vitro experiments like quantitative real-time PCR analysis, western blot, immunofluorescence and ethynyl-20-deoxyuridine staining were performed to explore the function of exosomal miR-1297 on HSC activation and proliferation.

Research results

miR-1297 was obviously overexpressed in exosomes derived from lipotoxic hepatocytes. The lipotoxic hepatocyte-derived exosomal miR-1297 could promote the activation and proliferation of HSCs through the PTEN/PI3K/AKT signaling pathway.

Research conclusions

The lipotoxic hepatocyte-derived exosomal miR-1297 could accelerate the progression of metabolic-associated fatty liver disease in a cell model.

Research perspectives

This study provided some new evidence on the crosstalk between hepatocyte-secreted exosomes and HSC. miR-1297 may become a potential target for the treatment of metabolic-associated fatty liver disease.