Osteopontin Promotes Macrophage M1 Polarization by Activation of the JAK1/STAT1/HMGB1 Signaling Pathway in Nonalcoholic Fatty Liver Disease  

作　　者：Zhihao Xu Feiyang Xi Xinxin Deng Yuqi Ni Changqin Pu Dan Wang Weiming Lou Xufang Zeng Ning Su Chen Chen Ziqiang Zeng Libin Deng Meixiu Jiang 

机构地区：[1]The Institute of Translational Medicine,Nanchang University,Nanchang,Jiangxi,China [2]School of Pharmacy,Nanchang University,Nanchang,Jiangxi,China [3]Central Laboratory,Affiliated Jinhua Hospital,Zhejiang University School of Medicine,Jinhua,Zhejiang,China [4]Jiangxi Provincial Key Laboratory of Preventive Medicine,School of Public Health,Nanchang University,Nanchang,Jiangxi,China [5]School of Basic Medical Science,Nanchang University,Nanchang,Jiangxi,China

出　　处：《Journal of Clinical and Translational Hepatology》2023年第2期273-283,共11页临床与转化肝病杂志（英文版）

基　　金：supported by National Natural Science Foundation of China grants (81760089,82160094 to MJ,82060112 to LD);Jiangxi Provincial Department of Science and Technology,China (20202BAB206087 to MJ).

摘　　要：Background and Aims:Osteopontin(OPN)is reported to be associated with the pathogenesis of nonalcoholic fatty liver disease(NAFLD).However,the function of OPN in NAFLD is still inconclusive.Therefore,our aim in this study was to evaluate the role of OPN in NAFLD and clarify the involved mechanisms.Methods:We analyzed the expression change of OPN in NAFLD by bioinformatic analysis,qRT-PCR,western blotting and immunofluorescence staining.To clarify the role of OPN in NAFLD,the effect of OPN from HepG2 cells on macrophage polarization and the involved mechanisms were examined by FACS and western blotting.Results:OPN was significantly upregulated in NAFLD patients compared with normal volunteers by microarray data,and the high expression of OPN was related with disease stage and progression.OPN level was also significantly increased in liver tissue samples of NAFLD from human and mouse,and in HepG2 cells treated with oleic acid(OA).Furthermore,the supernatants of OPN-treated HepG2 cells promoted the macrophage M1 polarization.Mechanistically,OPN activated the janus kinase 1(JAK1)/signal transducers and activators of transcription 1(STAT1)signaling pathway in HepG2 cells,and consequently HepG2 cells secreted more high-mobility group box 1(HMGB1),thereby promoting macrophage M1 polarization.Conclusions:OPN promoted macrophage M1 polarization by increasing JAK1/STAT1-induced HMGB1 secretion in hepatocytes.

关 键 词：OPN NAFLD Macrophage M1 polarization HMGB1 JAK1/STAT1 signaling 

分 类 号：R575.5[医药卫生—消化系统]