USP19 Stabilizes TAK1 to Regulate High Glucose/Free Fatty Acid-induced Dysfunction in HK-2 Cells  

作　　者：Xiao-hui YAN Yin-na ZHU Yan-ting ZHU 

机构地区：[1]Kidney Disease and Dialysis Center,Shaanxi Provincial People's Hospital,Xi'an 710068,China [2]Department of Nephrology,The Third Affiliated Hospital of Xi'an Medical University,Xi'an 710000,China [3]Nephrology and Hemodialysis Center,Shaanxi Provincial People's Hospital,Xi'an 710068,China

出　　处：《Current Medical Science》2024年第4期707-717,共11页当代医学科学（英文）

基　　金：supported by Natural Science Foundation of Shaanxi Province(No.2023-JC-YB-743 and No.2021JQ-905).

摘　　要：Objective Obesity-induced kidney injury contributes to the development of diabetic nephropathy(DN).Here,we identified the functions of ubiquitin-specific peptidase 19(USP19)in HK-2 cells exposed to a combination of high glucose(HG)and free fatty acid(FFA)and determined its association with TGF-beta-activated kinase 1(TAK1).Methods HK-2 cells were exposed to a combination of HG and FFA.USP19 mRNA expression was detected by quantitative RT-PCR(qRT-PCR),and protein analysis was performed by immunoblotting(IB).Cell growth was assessed by Cell Counting Kit-8(CCK-8)viability and 5-ethynyl-2′-deoxyuridine(EdU)proliferation assays.Cell cycle distribution and apoptosis were detected by flow cytometry.The USP19/TAK1 interaction and ubiquitinated TAK1 levels were assayed by coimmunoprecipitation(Co-IP)assays and IB.Results In HG+FFA-challenged HK-2 cells,USP19 was highly expressed.USP19 knockdown attenuated HG+FFA-triggered growth inhibition and apoptosis promotion in HK-2 cells.Moreover,USP19 knockdown alleviated HG+FFA-mediated PTEN-induced putative kinase 1(PINK1)/Parkin pathway inactivation and increased mitochondrial reactive oxygen species(ROS)generation in HK-2 cells.Mechanistically,USP19 stabilized the TAK1 protein through deubiquitination.Importantly,increased TAK1 expression reversed the USP19 knockdown-mediated phenotypic changes and PINK1/Parkin pathway activation in HG+FFA-challenged HK-2 cells.Conclusion The findings revealed that USP19 plays a crucial role in promoting HK-2 cell dysfunction induced by combined stimulation with HG and FFAs by stabilizing TAK1,providing a potential therapeutic strategy for combating DN.

关 键 词：HK-2 cells high glucose free fatty acid DYSFUNCTION USP19 DEUBIQUITINATION 

分 类 号：R587.1[医药卫生—内分泌] R692[医药卫生—内科学]