Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury  

作　　者：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 

机构地区：[1]Department of Infectious Diseases,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,Guizhou Province,China [2]Department of Infectious Diseases,Jingmen Central Hospital,Jingmen 448000,Hubei Province,China [3]Department of Respiratory Medicine,Anshun People’s Hospital,Anshun 561099,Guizhou Province,China [4]Department of General Practice,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,Guizhou Province,China [5]Department of Intervention Radiology,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,Guizhou Province,China [6]School of Public Health,Zunyi Medical University,Zunyi 563099,Guizhou Province,China [7]Department of Liver Diseases,Third People’s Hospital of Changzhou,Changzhou 213000,Jiangsu Province,China [8]Department of Digestion,Dafang County People’s Hospital,Bijie 551600,Guizhou Province,China

出　　处：《World Journal of Gastroenterology》2024年第9期1189-1212,共24页世界胃肠病学杂志（英文版）

基　　金：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;Bijie City Science and Planning Bureau,No.BKH(2022)8.

摘　　要：BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances.However,its contribution to the progression of liver damage remains unclear.AIM To determine the role and mechanism of UGT1A1 in liver damage progression.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.RESULTS Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis.This suggests that low UGT1A1 levels may be associated with the progression of liver damage.In mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be increased.In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ACLF.UGT1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid metabolism.CONCLUSION UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver injury.UGT1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.

关 键 词：Uridine diphosphate glucuronosyltransferase 1A1 Liver injury progression Endoplasmic reticulum stress Oxidative stress Lipid metabolism disorders 

分 类 号：R575[医药卫生—消化系统]