NR4A1 silencing alleviates high-glucose-stimulated HK-2 cells pyroptosis and fibrosis via hindering NLRP3 activation and PI3K/AKT pathway  

作　　者：Jin-Meng Li Zi-Hua Song Yuan Li Han-Wen Chen Han Li Lu Yuan Jing Li Wen-Yue Lv Lei Liu Na Wang 

机构地区：[1]Department of Clinical Medicine,Jining Medical University,Jining 272013,Shandong Province,China [2]Department of General Medicine,Affiliated Hospital of Jining Medical University,Jining 272029,Shandong Province,China

出　　处：《World Journal of Diabetes》2025年第3期203-215,共13页世界糖尿病杂志(英文)

基　　金：Supported by Research Fund for Academician Lin He New Medicine,No.JYHL2022FMS02.

摘　　要：BACKGROUND The pathophysiology of diabetic kidney disease(DKD)is complex.Interfering with the processes of pyroptosis and fibrosis is an effective strategy for slowing DKD progression.Previous studies have revealed that nuclear receptor subfamily 4 group A member 1(NR4A1)may serve as a novel pathogenic element in DKD;however,the specific mechanism by which it contributes to pyroptosis and fibrosis in DKD is unknown.AIM To investigate the role of NR4A1 in renal pyroptosis and fibrosis in DKD and possible molecular mechanisms.METHODS Streptozotocin 60 mg/kg was injected intraperitoneally to establish a rat model of DKD.Typically,45 mmol/L glucose[high glucose(HG)]was used to activate HK-2 cells to mimic the DKD model in vitro.HK-2 cells were transfected with NR4A1 siRNA to silence NR4A1.RESULTS NR4A1 was elevated in renal tissues of DKD rats and HG-stimulated HK-2 cells.Concurrently,NOD-like receptor protein 3(NLRP3)and phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathways were triggered,and pyroptosis and expression of fibrosis-linked elements was increased in vivo and in vitro.These alterations were significantly reversed via NR4A1 silencing.CONCLUSION Inhibition of NR4A1 mitigated pyroptosis and fibrosis via suppressing NLRP3 activation and the PI3K/AKT pathway in HG-activated HK-2 cells.

关 键 词：Diabetes Diabetic kidney disease PYROPTOSIS FIBROSIS Nuclear receptor subfamily 4 group A member 1 

分 类 号：R587.1[医药卫生—内分泌]