β-Arrestin-2 enhances endoplasmic reticulum stress-induced glomerular endothelial cell injury by activating transcription factor 6 in diabetic nephropathy  

作　　者：Jiang Liu Xiao-Yun Song Xiu-Ting Li Mu Yang Fang Wang Ying Han Ying Jiang Yu-Xin Lei Miao Jiang Wen Zhang Dong-Qi Tang 

机构地区：[1]Center for Gene and Immunotherapy,Institute of Medical Sciences,The Second Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250033,Shandong Province,China [2]Center for Gene and Immunotherapy,Cheeloo College of Medicine,Shandong University,Jinan 250033,Shandong Province,China [3]Medical Device and Pharmaceutical Packaging Inspection,Shandong Institute of Medical Device and Pharmaceutical Packaging Inspection,Jinan 250101,Shandong Province,China [4]Center of Animal,Institute of Medical Sciences,The Second Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250033,Shandong Province,China [5]Clinical Skill Training Centre,The Second Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250033,Shandong Province,China

出　　处：《World Journal of Diabetes》2024年第12期2322-2337,共16页世界糖尿病杂志（英文）

基　　金：Supported by Key Research and Development Program of Shandong Province,No.2021CXGC011101;Special Fund for Taishan Scholars Project,No.tsqn202211324;National Natural Science Foundation of China,No.81900669;Natural Science Foundation of Shandong Province,China,No.ZR2018PH007;the Multidisciplinary Innovation Center for Nephrology of the Second Hospital of Shandong University.

摘　　要：BACKGROUND Glomerular endothelial cell(GENC)injury is a characteristic of early-stage diabetic nephropathy(DN),and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importance.AIM To investigate the role ofβ-arrestin-2 in GENCs under DN conditions.METHODS Eight-week-old C57BL/6J mice were intraperitoneally injected with streptozotocin to induce DN.GENCs were transfected with plasmids containing siRNA-β-arrestin-2,shRNA-activating transcription factor 6(ATF6),pCDNA-β-arrestin-2,or pCDNA-ATF6.Additionally,adeno-associated virus(AAV)containing shRNA-β-arrestin-2 was administered via a tail vein injection in DN mice.RESULTS The upregulation ofβ-arrestin-2 was observed in patients with DN as well as in GENCs from DN mice.Knockdown ofβ-arrestin-2 reduced apoptosis in high glucose-treated GENCs,which was reversed by the overexpression of ATF6.Moreover,overexpression ofβ-arrestin-2 Led to the activation of endoplasmic reticulum(ER)stress and the apoptosis of GENCs which could be mitigated by silencing of ATF6.Furthermore,knockdown ofβ-arrestin-2 by the administration of AAV-shRNA-β-arrestin-2 alleviated renal injury in DN mice.CONCLUSION Knockdown ofβ-arrestin-2 prevents GENC apoptosis by inhibiting ATF6-mediated ER stress in vivo and in vitro.Consequently,β-arrestin-2 may represent a promising therapeutic target for the clinical management of patients with DN.

关 键 词：Diabetic nephropathy Glomerular endothelial cell β-Arrestin-2 Activating transcription factor 6 Endoplasmic reticulum stress 

分 类 号：R965[医药卫生—药理学]