Li WY, Yang F, Li X, Wang LW, Wang Y. Stress granules inhibit endoplasmic reticulum stress-mediated apoptosis during hypoxia-induced injury in acute liver failure. World J Gastroenterol 2023; 29(8): 1315-1329 [PMID: 36925453 DOI: 10.3748/wjg.v29.i8.1315]
Corresponding Author of This Article
Yao Wang, Doctor, Chief Physician, Department of Infectious Diseases, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan 430060, Hubei Province, China. rm003743@whu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
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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/
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Li WY, Yang F, Li X, Wang LW, Wang Y. Stress granules inhibit endoplasmic reticulum stress-mediated apoptosis during hypoxia-induced injury in acute liver failure. World J Gastroenterol 2023; 29(8): 1315-1329 [PMID: 36925453 DOI: 10.3748/wjg.v29.i8.1315]
World J Gastroenterol. Feb 28, 2023; 29(8): 1315-1329 Published online Feb 28, 2023. doi: 10.3748/wjg.v29.i8.1315
Stress granules inhibit endoplasmic reticulum stress-mediated apoptosis during hypoxia-induced injury in acute liver failure
Wen-Yuan Li, Fan Yang, Xun Li, Lu-Wen Wang, Yao Wang
Wen-Yuan Li, Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Fan Yang, Xun Li, Lu-Wen Wang, Yao Wang, Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Author contributions: Wang Y takes responsibility for the integrity of the work as a whole, from inception to published article; Wang Y and Li WY conceived and designed the study; Li WY, Yang F, Li X and Wang LW perform the experiment; Li WY and Wang Y wrote the paper; Wang Y edited the article; all authors approved the final version of the manuscript.
Supported bythe National Natural Science Foundation of China, No. 82100630 and No. 82100894; and the Fundamental Research Funds for the Central Universities, No. 2042021kf0080.
Institutional animal care and use committee statement: All animal operations were approved by the Animal Care and Use Committee of Renmin Hospital of Wuhan University, China (Approve number: WDRY2021-K016).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All datasets generated for this study are included in the article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yao Wang, Doctor, Chief Physician, Department of Infectious Diseases, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan 430060, Hubei Province, China. rm003743@whu.edu.cn
Received: November 3, 2022 Peer-review started: November 3, 2022 First decision: November 14, 2022 Revised: November 22, 2022 Accepted: February 16, 2023 Article in press: February 16, 2023 Published online: February 28, 2023 Processing time: 117 Days and 6.7 Hours
Abstract
BACKGROUND
Stress granules (SGs) could be formed under different stimulation to inhibit cell injury.
AIM
To investigate whether SGs could protect hepatocytes from hypoxia-induced damage during acute liver failure (ALF) by reducing endoplasmic reticulum stress (ERS) mediated apoptosis.
METHODS
The agonist of SGs, arsenite (Ars) was used to intervene hypoxia-induced hepatocyte injury cellular model and ALF mice models. Further, the siRNA of activating transcription factor 4 (ATF4) and SGs inhibitor anisomycin was then used to intervene in cell models.
RESULTS
With the increase of hypoxia time from 4 h to 12 h, the levels of HIF-1α, ERS and apoptosis gradually increased, and the expression of SGs marker G3BP1 and TIA-1 was increased and then decreased. Compared with the hypoxia cell model group and ALF mice model, the levels of HIF-1α, apoptosis and ERS were increased in the Ars intervention group. After siRNA-ATF4 intervention, the level of SGs in cells increased, and the levels of HIF-1α, ERS and apoptosis decreased. Compared with the siRNA-ATF4 group, the levels of G3BP1 in the siRNA-ATF4+anisomycin group were decreased, and the levels of HIF-1α, ERS and apoptosis were increased. Moreover, compared with the ALF group, the degree of liver injury and liver function, the levels of HIF-1α, ERS and apoptosis in the Ars intervention group were decreased, the level of SGs was increased.
CONCLUSION
SGs could protect hepatocytes from hypoxia-induced damage during ALF by reducing ERS-mediated apoptosis.
Core Tip: Hepatocytes were damaged by hypoxia and ischemia injury in the process of acute liver failure. At this time, the content of HIF-1α in cells increased, which inhibited the formation of stress granules (SGs) mediated by G3BP1 and promoted the expression of endoplasmic reticulum stress (ERS) marker molecules activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-homologous protein. The activated ERS pathway further promotes hepatocyte apoptosis. Promoting SGs synthesis can inhibit the level of hepatocyte apoptosis by inhibiting the ATF4-mediated ERS pathway.
