糖尿病肾脏疾病中肾小球相关差异表达基因的生物信息学分析

Bioinformatics Analysis of Glomerular Related Differentially Expressed Genes in Diabetic Kidney Disease

目的分析糖尿病肾脏疾病(DKD)中肾小球相关差异表达基因(DEGs)的生物学功能和潜在机制。方法从GEO数据库中筛选得到与DKD肾小球相关的GSE30528和GSE1009两个数据集,利用GEO2R在线分析软件获得DEGs,并通过韦恩图获得重叠的DEGs,采用生物信息学软件进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,并建立微RNA(miRNA)-DEGs网络和蛋白质-蛋白质相互作用(PPI)网络,利用Cytoscape软件筛选核心基因。结果在GSE30528中筛选获得632个DEGs,在GSE1009中获得49个DEGs,随后2个数据集取交集共获得26个重叠的DEGs。GO富集分析结果显示,重叠的DEGs主要表现在肾脏和泌尿系统的形成、细胞的迁移等生物过程上,板状伪足、细胞前缘、肌动蛋白细胞骨架等细胞成分上,磷酸酯水解酶活性、蛋白质同型二聚化活性等分子功能上。KEGG结果显示,重叠的DEGs主要调节晚期糖基化终末产物-晚期糖基化终末产物受体信号通路、Rap1信号通路和钙信号通路等7条信号通路。通过PPI网络和Cytoscape软件筛选得到重叠的DEGs中排名前5的关键基因为血管内皮生长因子A(VEGFA)、信号素5A、1型血小板反应蛋白7A域、磷脂酶A 2受体1、叉头框蛋白C1,其中VEGFA为核心基因;miRNA-DEGs网络显示,miR-17-5p和miR-20a-5p靶向包括VEGFA在内的6个重叠DEGs。结论利用生物学信息方法分析肾小球相关的DEGs有助于理解DKD进展的分子机制,miR-17-5p和miR-20a-5p-VEGFA可能通过介导肾小球病变参与正常白蛋白尿DKD的产生。

Objective To analyze the biological function and potential mechanism of glomerular related differentially expressed genes(DEGs)in diabetic kidney disease(DKD).Methods GSE30528 and GSE1009 data sets related to DKD glomeruli were screened from GEO database,and DEGs were obtained by GEO2R online analysis software,and then overlapping DEGs were obtained by Venn diagram.The bioinformatics software was adopted for Gene Ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.And microRNA(miRNA)-DEGs network and protein-protein interaction(PPI)network were established,and core genes were screened by Cytoscape software.Results Altogether 632 DEGs were obtained in GSE30528,and 49 DEGs were obtained in GSE1009.Then a total of 26 overlapped DEGs were gained from the intersection of the two datasets.The results of GO enrichment analysis showed that the overlapped DEGs were mainly manifested in the development of nephron and urogenital system,cell migration and other biological processes,lamellipodium,cell leading edge,actin cytoskeleton and other cellular components,phosphoric ester hydrolase activity,protein homodimerization activity and other molecular functions.The results of KEGG enrichment analysis showed that the overlapped DEGs mainly regulated seven signaling pathways including advanced glycation end product-receptor for advanced glycation end product signaling pathway,Rap1 signaling pathway and calcium signaling pathway etc.Vascular endothelial growth factor A(VEGFA),semaphorin 5A,thrombospondin type-1 domain-containing 7A,phospholipase A 2 receptor 1 and forkhead box protein C1 were selected as the top 5 key genes of overlapping DEGs by PPI network and Cytoscape software,among which VEGFA was the core gene.The miRNA-DEGs network showed that miR-17-5p and miR-20a-5p targeted six overlapping DEGs including VEGFA.Conclusion The analysis of glomerulus-related DEGs by biological information method is helpful to understand the molecular mechanism of DKD progression.MiR-17-5p and miR-20a-5p-VEGFA may participate in the production of normal albuminuria DKD by mediating glomerular lesions.