Tumor necrosis factor-α signaling in nonalcoholic steatohepatitis and targeted therapies

作     者：Sijia Lu Yibing Wang Junli Liu Sijia Lu;Yibing Wang;Junli Liu

作者机构：Shanghai Diabetes InstituteDepartment of Endocrinology and MetabolismShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China School of KinesiologyShanghai University of SportsShanghai 200438China 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2022年第49卷第4期

页      面：269-278页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 10[医学] 

基　　金：supported by the following grants to J. L.: National Key R&D Program of China (2018YFA0800600) National Natural Science Foundation of China (81770797) National Science Fund for Excellent Young Scholars (31722028) Open Project of State Key Laboratory of Natural Medicines China Pharmaceutical University (SKLNMKF201706, SKLNMZZCX201820) Shanghai Municipal Commission of Science and Technology (20410713200) National Facility for Translational Medicine (Shanghai) (TMSK-2020-102) “Shuguang Program” supported by Shanghai Education Development Foundation Shanghai Municipal Education Commission (20SG10) 

主　　题：TNF-αsignaling NASH Inflammation Cell death Fibrosis 

摘      要：Nonalcoholic steatohepatitis(NASH),an inflammatory subtype of nonalcoholic fatty liver disease,is featured by significantly elevated levels of various proinflammatory cytokines.Among numerous proinflammatory factors that contribute to NASH pathogenesis,the secreted protein,tumor necrosis factoralpha(TNF-α),plays an essential role in multiple facets of NASH progression and is therefore considered as a potential therapeutic target.In this review,we will first systematically describe the preclinical studies on the biochemical function of TNF-αand its intracellular downstream signaling mechanisms through its receptors.Moreover,we extensively discuss its functions in regulating inflammation,cell death,and fibrosis of liver cells in the pathogenesis of NASH,and the molecular mechanism that TNF-αexpression is regulated by NF-κB and other upstream master regulators during NASH progression.As TNF-αis one of the causal factors that remarkably contributes to NASH progression,combination of therapeutic modalities,including TNF-α-based therapies may lead to the resolution of NASH via multiple pathways and thus generate clinical benefits.For translational studies,we summarize recent advances in strategies targeting TNF-αand its signaling pathway,which paves the way for potential therapeutic treatments for NASH in the future.