激光生物学报2024，Vol.33Issue(2)：176-184,9.DOI:10.3969/j.issn.1007-7146.2024.02.010
基于高尿酸诱导的NRK-52E细胞模型探讨ZAG与ERK1/2和p38信号通路的交互作用
Investigation of the Interaction of ZAG with ERK1/2 and p38 Signaling Pathways Based on the NRK-52E Cell Model Induced by High Uric Acid
摘要
Abstract
The aim of this paper is to explore the mechanism of zinc-α2-glycoprotein(ZAG)forming a feedback pathway with extracellular signal-regulated kinase 1/2(ERK1/2)and p38 to regulate epithelial mesenchymal transition(EMT)in rat re-nal epithelial cells(NRK-52E)induced by high uric acid environment,we divided NRK-52E into normal control group and high uric acid-induced group which was stimulated by 20 mg/dL uric acid for 48 h,and the cells in each group were transfected with overexpression of ZAG and knocked down respectively,to observe the interactions between ZAG expression level and ERK1/2 and p38 signaling pathways in the cells.The results revealed that the mRNA and protein expression of EMT-related molecules were elevated in rat kidney cells under high uric acid environment compared with the normal culture group(P<0.05);up-reg-ulation of ZAG decreased the expression of mitogen-activated protein kinase kinase(MAPKK),ERK1/2,p38,activated tran-scription factor-2(ATF2)and protein kinase B(PKB or Akt)mRNA in this pathway in rat kidney epithelial cells under high uric acid environment culture(P<0.01),while the downregulation of ZAG increased(P<0.05).At the protein level,the expression of MAPKK,p38 and Akt decreased in the ZAG up-regulated group compared to the untransfected group(P<0.05,P<0.01,P<0.001);and the expression of ERK1/2,p38 and Akt was elevated in the ZAG down-regulated group(P<0.001,P<0.05,P<0.01).The results suggest that transfection up-regulation of ZAG decreases the expression of laminin and vimentin mRNA,the marker genes related to EMT in NRK-52E;regulation of ZAG expression in NRK-52E can play a positive role in ERK1/2 and p38 signaling pathways,and thus inhibit renal cell EMT.This study provides an experimental basis for clinical treatment of hyperuricemic nephropathy(HN).关键词
肾纤维化/上皮细胞间充质转化/尿酸性肾病/高尿酸/锌α2糖蛋白Key words
nephrofibrotic:epithelial mesenchymal transformation of urine/uric acid nephropathy/hyperuricemia/zinc-α2-glycoprotein分类
医药卫生引用本文复制引用
陈柄源,杨洁,樊凯璇,陈秉朴..基于高尿酸诱导的NRK-52E细胞模型探讨ZAG与ERK1/2和p38信号通路的交互作用[J].激光生物学报,2024,33(2):176-184,9.基金项目
广西自然科学基金项目(2020GXNSFAA297151) （2020GXNSFAA297151）
右江民族医学院高层次人才科研项目(RZ2100000455) （RZ2100000455）
广西高校中青年教师科研基础能力提升项目(2021KY0554). （2021KY0554）
