RNA m6A甲基转移酶METTL3在AngⅡ诱导的HK-2细胞损伤中的作用初探  

Role of RNA m6A methyltransferase METTL3 in AngⅡ-induced HK-2 cell injury

作　　者：余春华[1] 李晗 余淑华 YU Chun-hua;LI Han;YU Shu-hua(Department of Geriatrics,the Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou 450007,China;Department of Hypertension,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450007,China)

机构地区：[1]郑州大学第五附属医院老年医学科,郑州450007 [2]郑州大学附属郑州中心医院高血压科,郑州450007

出　　处：《医药论坛杂志》2024年第20期2129-2134,共6页Journal of Medical Forum

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20210776)。

摘　　要：目的利用血管紧张素II(angiotensin II,AngⅡ)诱导的人肾小管上皮细胞(human kideny-2,HK-2)细胞损伤模型明确甲基转移酶样因子3(methyltransferase-like 3,METTL3)在高血压肾损伤中的作用并探讨相关分子机制。方法选择5*10-4M AngⅡ刺激HK-2细胞48 h构建高血压肾损伤细胞模型,分为对照组、5*10-4M AngⅡ组、siMETTL3组、siMETTL3+AngⅡ组,研究AngⅡ刺激HK-2细胞后METTL3 mRNA及蛋白表达的影响及细胞的增殖与凋亡情况。结果与对照组相比,AngⅡ能够显著增高HK-2细胞中METTL3蛋白及mRNA的表达(P<0.01);敲低METTL3后,siMETTL3+AngⅡ组的中METTL3蛋白及mRNA整体水平较AngⅡ组降低(P<0.05),且siMETTL3+AngⅡ组的HK-2细胞较AngⅡ组增殖减少,凋亡增加。结论METTL3可能具有保护肾小管上皮细胞免受损伤的作用,加药后引起细胞损伤,诱导METTL3保护性升高,加药后同时敲低保护蛋白METTL3导致细胞进一步的损伤。Objective To investigate the role of methyltransferase-like factor 3(METTL3)in hypertensive renal injury by using angiotensin II(Ang II)induced human kideny-2(HK-2)cell injury model and explore the related molecular mechanism.Methods HK-2 cells were stimulated by 5*10-4M AngⅡfor 48 h to construct the hypertensive renal injury cell model,which was divided into control group,5*10-4M AngⅡgroup,siMETTL3 group and siMETTL3+AngⅡgroup.To study the effect of AngⅡstimulation on METTL3 mRNA and protein expression and cell proliferation and apoptosis in HK-2 cells.Results AngⅡcould significantly increase the expression of METTL3 protein and mRNA in HK-2 cells compared with control group(P<0.01).After METTL3 knockdown,the overall levels of METTL3 protein and mRNA in siMETTL3+AngⅡgroup were lower than those in AngⅡgroup(P<0.05),and HK-2 cells in siMETTL3+AngⅡgroup were less proliferating and more apoptotic than those in AngⅡgroup.Conclusion METTL3 may have a protective effect on renal tubular epithelial cells from injury.METTL3 may be damaged after administration,and the protective increase of METTL3 may be induced,while the protective protein METTL3 may be knocked down at the same time after administration,leading to further cell damage.

关 键 词：甲基转移酶样因子3 血管紧张素II 人肾小管上皮细胞 高血压肾损伤 

分 类 号：R544.1[医药卫生—心血管疾病]