USP10 Alleviates Palmitic Acid-induced Steatosis through Autophagy in HepG2 Cells  

作　　者：Sheng-Liang Xin Xiao-Li Pan Xiao-Yuan Xu Yan-Yan Yu 

机构地区：[1]Department of Infectious Diseases,Peking University First Hospital,Beijing,China [2]Division of Gastroenterology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China

出　　处：《Journal of Clinical and Translational Hepatology》2023年第1期45-57,共13页临床与转化肝病杂志（英文版）

摘　　要：Background and Aims:Nonalcoholic fatty liver disease(NAFLD)is a common chronic liver disease caused by overnutrition.Impaired autophagy is closely related to NAFLD progression.Recently,ubiquitin-specific peptidase-10(USP10)was reported to ameliorate hepatic steatosis,but the underlying mechanism is still unclear.In view of the potential effects of USP10 on autophagy,we investigated whether USP10 alleviated steatosis through autophagy.Methods:HepG2 cells were treated with palmitic acid(PA)to model NAFLD in vitro.Lentivirus was used to regulate USP10 level in cells.Autophagic regulators were used to autophagic progression in cells.Western blotting,real-time fluorescence quantitative polymerase chain reaction,lipid drop staining and immunofluorescent staining were performed to determine the effect of USP10 on lipid autophagy.Student’s t-test and Tukey’s post hoc test were used to compare the means among groups.Results:PA induced cellular steatosis with dependance on autophagy.USP10 overexpression alleviated PA-induced steatosis,restored autophagic activity,promoted autophagic flux,including synthesis and degradation of autophagosomes,and lipid-targeted autophagy.In the presence of autophagy inhibitors,the protective effectiveness of USP10 on steatosis decreased.Furthermore,the specific inhibitor to C-jun N-terminal protein kinase-1(JNK1),DB07268,abolished USP10-induced autophagy.However,during early stage inhibition of JNK1,compensatory expression of tuberous sclerosis complex-2(TSC2)maintained autophagy.The degree of TSC2-to-JNK1 compensation was positively associated with USP10 level.Functionally,JNK1 and TSC2 were involved in the lipid-lowering effect of USP10.Conclusions:USP10 alleviated hepatocellular steatosis in autophagy-dependent manner.JNK1/TSC2 signaling pathways were required for USP10-induced autophagy.

关 键 词：AUTOPHAGY Nonalcoholic fatty liver disease STEATOSIS Ubiquitinspecific peptidase-10 C-jun N-terminal protein kinase-1 Tuberous sclerosis complex-2 

分 类 号：R285[医药卫生—中药学]