糖尿病肾病相关基因筛选及生物信息学分析

Screening and bioinformatics analysis of diabetic nephropathy-related genes

目的采用生物信息学技术筛选糖尿病肾病(DN)相关基因并预测其生物学功能、信号通路。方法在基因公共表达数据库(GEO)中筛选并下载DN相关基因芯片数据,采用GEO在线分析软件GEO2R分析在DN肾组织与正常肾组织中差异表达的基因。对筛选出的差异表达基因进行基因本体论(GO)分析和京都基因与基因组百科全书(KEEG)分析,预测基因功能及参与的信号通路。采用蛋白-蛋白相互作用数据库(STRING)分析差异表达基因编码蛋白间的相互作用关系。结果筛选出9个差异表达最为显著的基因,分别为PLCE1、CLIC5、PTPRO、热休克蛋白A12A(HSPA12A)、AIF1、GMDS、SEMA5A、CEP152、FOXC1。除CEP152表达下调外,余8个基因在DN组表达上调。差异表达基因的主要分子功能涉及蛋白结合、对细胞刺激反应和细胞信号转导,主要调控细胞代谢等生物学过程。差异表达基因主要参与细胞代谢途径、甲状腺激素信号通路、Rap1信号通路、磷脂酰肌醇信号系统及肌醇磷酸代谢等信号通路。蛋白网络分析提示HSPA12A、GMDS、CEP152基因编码蛋白与其他蛋白作用关联最紧密,为蛋白-蛋白相互作用网络的中心节点。结论筛选出了9个在DN肾组织与正常肾组织中差异表达最显著的基因,其靶基因功能涉及蛋白结合、对细胞刺激反应和细胞信号转导,主要调控细胞代谢等生物学过程。HSPA12A、GMDS、CEP152基因可能是DN的关键基因,其异常表达可能共同参与了DN的发病。

Objective To screen out the related genes of diabetic nephropathy(DN)and to predict their biological functions and signaling pathways by using bioinformatics analysis.Methods Gene microarray data-related to DN were screened and downloaded from the Gene Common Expression Database(GEO).Differentially expressed genes were analyzed by GEO online analysis software GEO2 R.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEEG)were used to analyze the differentially expressed genes and then we predicted their possible functions and signaling pathways.The protein-protein interaction database(STRING)was used to analyze the interaction between proteins encoded by differentially expressed genes.Results The most significant 9 genes,including PLCE,CLIC5,PTPRO,HSPA12 A,AIF1,GMDS,SEMA5 A,CEP152,and FOXC1,were differentially expressed in GSE1009 data.Except for CEP152,the left 8 genes were all up-regulated in the DN group.The main molecular functions of differentially expressed genes were involved in protein binding,cell stimulation,and cell signal transduction,and they mainly regulated biological processes such as cell metabolism.Differentially expressed genes were mainly involved in the metabolic pathways,thyroid hormone signaling,Rap1 signaling,phosphatidylinositol signaling and inositol phosphate metabolism pathway.Protein network analysis indicated that HSPA12 A,GMDS,CEP152 gene coding proteins were most closely related to other proteins and were the central nodes of protein-protein interaction network.Conclusions Nine differentially expressed genes in DN and normal kidney tissues are screened out.The target genes are involved in the protein binding,cell stimulus response and cell signal transduction,and mainly regulate the cell metabolism biological processes.HSPA12 A,GMDS and CEP152 genes may be the key genes of DN,and their abnormal expression may be involved in the pathogenesis of DN.