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 th...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.展开更多
文摘目的探讨血清CXC趋化因子受体4(CXC chemokine receptor 4,CXCR4)、趋化因子3(C-C Motif Chemokine3,CCL3)、趋化素样因子-1(chemokine like factor-1,CKLF-1)水平与支气管哮喘患儿肺功能的相关性。方法选取我院2021年6月至2023年6月收治的103例支气管哮喘患儿为观察组,同期103例健康体检儿童为对照组。比较两组入院时血清CXCR4、CCL3、CKLF-1水平及肺功能指标[第1秒用力呼气容积(forced expiratory volume in one second,FEV1)、呼气峰值流速占比预计值百分比(peak expiratory flow,PEF)、第1秒用力呼气容积/用力肺活量(forced expiratory volume in one second/forced vital capacity,FEV1/FVC)、用力肺活量(forced vital capacity,FVC)],采用Pearson分析相关性,采用绘制受试者工作特征(ROC)分析联合诊断价值。结果观察组血清CXCR4、CCL3、CKLF-1水平高于对照组(t_(1)=44.430;t_(2)=22.036;t_(3)=26.314,P<0.05);观察组PEF、FEV_(1)、FVC、FEV_(1)/FVC水平低于对照组(t_(1)=19.329;t_(2)=19.524;t_(3)=11.088;t_(4)=25.812,P<0.05);血清CXCR4、CCL3、CKLF-1水平与PEF、FEV_(1)、FVC、FEV_(1)/FVC均呈负相关(P<0.05);联合诊断最佳敏感度、特异度为92.23%、72.82%。结论血清CXCR4、CCL3、CKLF-1水平与疾病密切相关,可作为临床诊断疾病的重要依据。
基金Supported by Research Fund for Academician Lin He New Medicine,No.JYHL2022FMS02.
文摘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.
