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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury
Jin-Lian Jiang, Yi-Yang Zhou, Wei-Wei Zhong, Lin-Yan Luo, Si-Ying Liu, Xiao-Yu Xie, Mao-Yuan Mu, Zhi-Gang Jiang, Yuan Xue, Jian Zhang, Yi-Huai He
Jin-Lian Jiang, Yi-Yang Zhou, Si-Ying Liu, Yi-Huai He, Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
Wei-Wei Zhong, Department of Infectious Diseases, Jingmen Central Hospital, Jingmen 448000, Hubei Province, China
Lin-Yan Luo, Department of Respiratory Medicine, Anshun People’s Hospital, Anshun 561099, Guizhou Province, China
Xiao-Yu Xie, Department of General Practice, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
Mao-Yuan Mu, Department of Intervention Radiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
Zhi-Gang Jiang, School of Public Health, Zunyi Medical University, Zunyi 563099, Guizhou Province, China
Yuan Xue, Department of Liver Diseases, Third People’s Hospital of Changzhou, Changzhou 213000, Jiangsu Province, China
Jian Zhang, Department of Digestion, Dafang County People’s Hospital, Bijie 551600, Guizhou Province, China
Co-first authors: Jin-Lian Jiang and Yi-Yang Zhou.
Author contributions: Jiang JL and Zhou YY contributed equally to this work; Jiang JL, Zhou YY, and He YH conceived and designed the research; Jiang JL, Zhou YY, Zhong WW, Luo LY, Liu SY, and Xie XY collected data and conducted research; Jiang JL, Zhou YY, Mu MY, Jiang ZG, Xue Y, and Zhang J analyzed and interpreted data; Jiang JL and Zhou YY wrote the initial draft; He YH revised the manuscript; and all authors read and approved the final version of the manuscript.
Supported by the Science and Technology Research Foundations of Guizhou Province, No. QKHJC-ZK(2022)YB642; Zunyi Science and Technology Plan Project, No. ZSKHHZ(2022)344, No. ZSKHHZ(2022)360, and No. ZYK160; Hubei Province Central Leading Local Science and Technology Development Special Project, No. 2022BCE030; Changzhou Science and Technology Projects, No. CE20225054; and Bijie City Science and Planning Bureau, No. BKH(2022)8.
Institutional review board statement: The study was reviewed and approved by the Zunyi Medical University Medical Ethics Review Committee [Approval No. ZYFYLS (2018)28 and No. ZYLS(2022)1-059].
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Affidavit of Approval of Animal Welfare and Ethical of Zunyi Medical University (Approval No. ZMU21-2107-003 and No. ZMU11-2203-314).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
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: Yi-Huai He, MD, Director, Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, No. 149 Dalian Road, Zunyi 563000, Guizhou Province, China. 993565989@qq.com
Received: September 28, 2023
Peer-review started: September 28, 2023
First decision: December 6, 2023
Revised: January 2, 2024
Accepted: January 29, 2024
Article in press: January 29, 2024
Published online: March 7, 2024
ARTICLE HIGHLIGHTS
Research background
Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is a member of the phase II metabolic enzyme family, which plays a significant role in metabolizing and detoxifying endogenous and exogenous substances. However, the role of UGT1A1 in liver disease remains controversial.
Research motivation
To determine the role and mechanism of UGT1A1 in the progression of liver injury.
Research objectives
To confirm that UGT1A1 prevents the progression of liver injury, and then elucidates the mechanism by which UGT1A1 delays the progression of liver damage from the viewpoints of endoplasmic reticulum (ER) stress, oxidative stress, and lipid metabolism disorder.
Research methods
We investigated the relationship between UGT1A1 expression and liver injury through clinical research. Additionally, the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study.
Research results
The expression of UGT1A1 in hepatocytes was upregulated as a compensatory response during liver injury. The upregulation of UGT1A1 was beneficial for hepatocytes to avoid apoptosis and necroptosis under conditions of ER stress, oxidative stress, and disrupted lipid metabolism. Disruption of this compensatory upregulation of UGT1A1 during liver injury could potentially expedite the progression of liver damage.
Research conclusions
UGT1A1 prevents the progression of liver injury by reducing hepatocyte apoptosis and necroptosis mediated by ER stress, oxidative stress, and lipid metabolism disorder.
Research perspectives
This study highlights the role of UGT1A1 in preventing the progression of liver injury. Further investigation is required to understand the specific mechanisms by which UGT1A1 regulates ER stress, oxidative stress, especially lipid metabolism, to hinder the progression of liver injury. The research findings enrich the understanding of the mechanism of liver injury progression and provide potential intervention targets for the treatment of liver injury.
