Dual roles of p62/SQSTM1 in the injury and recovery phases of acetaminophen-induced liver injury in mice

作     者：Hui Qian Qingyun Bai Xiao Yang Jephte Y.Akakpo Lili Ji Li Yang Thomas Rulicke Kurt Zatloukal Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Hui Qian;Qingyun Bai;Xiao Yang;Jephte Y.Akakpo;Lili Ji;Li Yang;Thomas Rülicke;Kurt Zatloukal;Hartmut Jaeschke;Hong-Min Ni;Wen-Xing Ding

作者机构：Department of PharmacologyToxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA The MOE Key Laboratory for Standardization of Chinese MedicinesShanghai Key Laboratory of Compound Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese MedicinesInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China School of Chemistry and BioengineeringYichun UniversityYichun 336000China Department of Biomedical SciencesUniversity of Veterinary Medicine Vienna Veterina¨rplatzVienna 1210Austria The Institute of PathologyMedical University of GrazGraz A-8036Austria 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第12期

页      面：3791-3805页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by fundings U01 AA024733 R37 AA020518 R21 AA027250 R01 DK102142 and R01 AG072895(USA) 

主　　题：Autophagy Coagulation DILI Liver regeneration Macrophage Hepatotoxicity Platelet 

摘      要：Acetaminophen(APAP)overdose can induce liver injury and is the most frequent cause of acute liver failure in the United *** investigated the role of p62/SQSTM1(referred to as p62)in APAP-induced liver injury(AILI)in *** found that the hepatic protein levels of p62 dramatically increased at 24 h after APAP treatment,which was inversely correlated with the hepatic levels of *** also activated mTOR at 24 h,which is associated with increased cell *** contrast,p62 knockout(KO)mice showed increased hepatic levels of APAP-adducts detected by a specific antibody using Western blot analysis but decreased mTOR activation and cell proliferation with aggravated liver injury at 24 h after APAP ***,p62 KO mice recovered from AILI whereas the wild-type mice still sustained liver injury at 48 *** found increased number of infiltrated macrophages in p62 KO mice that were accompanied with decreased hepatic von Willebrand factor(VWF)and platelet aggregation,which are associated with increased cell proliferation and improved liver injury at 48 h after APAP *** data indicate that p62 inhibits the late injury phase of AILI by increasing autophagic selective removal of APAP-adducts and mitochondria but impairs the recovery phase of AILI likely by enhancing hepatic blood coagulation.