Luo X, Luo SZ, Xu ZX, Zhou C, Li ZH, Zhou XY, Xu MY. Lipotoxic hepatocyte-derived exosomal miR-1297 promotes hepatic stellate cell activation through the PTEN signaling pathway in metabolic-associated fatty liver disease. World J Gastroenterol 2021; 27(14): 1419-1434 [PMID: 33911465 DOI: 10.3748/wjg.v27.i14.1419]
Corresponding Author of This Article
Ming-Yi Xu, MD, Chief Doctor, Professor, Department of Gastroenterology, Shanghai General Hospital, No. 100 Haining Road, Shanghai 200080, China. xumingyi2014@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
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 byThe 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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ming-Yi Xu, MD, Chief Doctor, Professor, Department of Gastroenterology, Shanghai General Hospital, No. 100 Haining Road, Shanghai 200080, China. xumingyi2014@163.com
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
ARTICLE HIGHLIGHTS
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.
