流体剪切力通过激活Piezo 1蛋白促进肾小球内皮细胞凋亡  

Fluid shear promotes apoptosis of glomerular endothelial cells by activation of Piezo 1

作　　者：罗梦琳 郑峰[4] 季欣瑶 祁彩虹 肖雨珩 牛长春 LUO Menglin;ZHENG Feng;JI Xinyao;QI Caihong;XIAO Yuheng;NIU Changchun(Department of Laboratory,the Affiliated Hospital of Southwest Medical University,Luzhou 646099;Department of Laboratory,Chongqing People′s Hospital,Chongqing 401121;Department of Laboratory,Qinghai Provincial People′s Hospital,Xining 810007,China;Department of Orthopedics,Qinghai Provincial People′s Hospital,Xining 810007,China)

机构地区：[1]西南医科大学附属医院检验科,四川泸州646099 [2]重庆市人民医院检验科,重庆401121 [3]青海省人民医院检验科,青海西宁810007 [4]青海省人民医院骨科,青海西宁810007

出　　处：《基础医学与临床》2024年第9期1236-1242,共7页Basic and Clinical Medicine

基　　金：青海省卫生健康委员会重点课题(2022-wjzd-02)。

摘　　要：目的探讨流体剪切力(FS)对肾小球内皮细胞(GECs)凋亡的影响及Piezo 1蛋白在其中的作用。方法对SD大鼠肾小球内皮细胞进行培养,使用Flexcell-T5000拉力仪模拟流体剪切力刺激,使用流式细胞测量技术检测细胞凋亡水平,通过免疫荧光染色试验检测Piezo 1蛋白在GECs中的表达水平。使用Ca 2+指示剂(Cal-590 AM)观察流体剪切力对Piezo 1通道的激活作用。使用化学激动剂Yoda1、抑制剂GsMtx 4及慢病毒Lv-shPiezo 1调控Piezo 1蛋白功能或表达后,观察Piezo 1对GECs凋亡的影响。结果与对照组相比,剪切力组细胞凋亡率增高(P<0.05),且随着流体剪切力强度升高,细胞凋亡率增高;Piezo 1在GECs中普遍表达,且流体剪切力可以激活Piezo 1通道并增强其表达;激动剂Yoda 1可以促进GECs的凋亡,抑制剂GsMtx 4可以抑制流体剪切力诱导的凋亡;Lv-shPiezo 1敲低GECs中Piezo 1的表达,且敲低组GECs的凋亡率较对照组及Lv-Ctrl组降低(P<0.05)。结论流体剪切力通过激活Piezo 1蛋白及增强其表达促进GECs的凋亡。Objective To investigate the effect of fluid shear(FS)on apoptosis of glomerular epithelial cells(GECs)and the role of Piezo 1 protein in it.Methods GECs(glomerular epithelial cells)of SD rat were cultured.Fluid shear stimulation was simulated by a Flexcell-T5000 tensiometer.Apoptosis level was detected by flow cytometry.The expression of Piezo 1 proteins in GECs was detected by immunofluorescence staining.The activating of Piezo 1 channels by fluid shear was observed using Ca 2+indicator(Cal-590 AM).The effect of Piezo 1 on apoptosis in GECs was analyzed after modulating the function or expression of Piezo 1 protein using the chemical activator Yoda1,the inhibitor GsMtx 4 was regulated by lentivirus Lv-shPiezo 1.Results Compared with the blank control group,apoptosis increased in the fluid shear group(P<0.05).The rate of apoptosis increased with the enhancing of fluid shear strength;Piezo 1 was commonly expressed in GECs.Fluid shear activated Piezo 1 channel and enhanced expression of Piezo 1.The agonist Yoda1 promoted the apoptosis of GECs GsMtx 4 inhibited the apoptosis induced by fluid shear.Lv-shPiezo 1 knocked down the expression of Piezo 1 in GECs and the apoptosis rate of GECs in the knockdown group was reduced as compared to that in the control group and Lv-Ctrl group(P<0.05).Conclusions Fluid shear may promote apoptosis of GECs by activation of Piezo 1 and by enhancing expression of Piezo 1.

关 键 词：流体剪切力 Piezo 1 肾小球内皮细胞 凋亡 Yoda 1 

分 类 号：R692.5[医药卫生—泌尿科学]