基于生物信息学分析早期糖尿病肾病发病机制  

Pathogenesis of early diabetic nephropathy:A bioinformatics analysis

作　　者：李英娜[1] 董兰 刘婉珊[1] 全林菲 何凤[1] LI Yingna;DONG Lan;LIU Wanshan;QUAN Linfei;HE Feng(Department of Nephrology,Guangzhou First People′s Hospital,Guangzhou 510180,China)

机构地区：[1]广州市第一人民医院肾内科,广州510180

出　　处：《实用医学杂志》2022年第14期1736-1742,共7页The Journal of Practical Medicine

基　　金：广州市科技计划项目(编号:201904010069)。

摘　　要：目的利用生物信息学筛选分析早期糖尿病肾病的差异基因表达,探讨糖尿病肾病发病机制并为其提供新的分子治疗靶点。方法通过GEO数据库获取数据集GSE142025行生物信息学分析,筛选早期糖尿病肾病组(e DN组)相对对照组(NC组)差异表达基因。GSEA分析差异表达基因的富集通路,通过蛋白质相互网络(PPI)分析鉴定HUB基因。采用免疫组化和RT-qPCR检测目标基因在肾组织中的相对表达水平。结果以P<0.05和|log2FC|>1为标准,筛选得到eDN组有1859个差异表达基因,其中有1063个上调,有796个下调。GSEA行差异基因的KEGG通路富集显示eDN组在“JAK-STAT通路”、“细胞因子受体通路”、“趋化因子信号通路”、“细胞黏附分子通路”、“细胞外基质受体相互作用通路”等显著上调。CCR2作为HUB基因在eDN组中表达显著上调;免疫组化及RT-qPCR结果显示一致,e DN组中CCR2相对表达水平明显高于NC组(均P<0.05)。结论KEGG分析功能富集主要显示炎症通路激活,而CCR2在早期糖尿病肾病的肾组织中表达显著上调,提示其可能在早期糖尿病肾病发生发展中起着重要作用。Objective To analyze and explore the differential gene expression and pathogenesis of early diabetic nephropathy with bioinformatics analysis,and to explore the pathogenesis of diabetic nephropathy and provide new molecular therapeutic targets for it.Methods In this study,the data set GSE142025 was obtained from the GEO database for bioinformatics analysis,and the differentially expressed genes were screened in the early diabetic nephropathy group(e DN group)when compared with those in normal control group(NC group).The enrichment pathways of differentially expressed genes were analyzed by GSEA,and HUB genes were identified by protein interaction network(PPI)analysis.The relative expression levels of target genes in kidney tissue were detected by immunohistochemistry and RT-qPCR.Results A total of 1,859 differentially expressed genes were screened using P<0.05 and|log2FC|>1 as the criteria in the e DN group.Among them,the expression of 1,063was up-regulated and that of 796 down-regulated.The KEGG pathway enrichment of differential genes in GSEA showed that the eDN group weresignificantly up-regulated in the“JAK-STAT pathway”,“Cytokine receptor pathway”,“Chemokine signaling pathway”,“Cell adhesion molecule pathway”,and“Extracellular matrix receptor interaction”.As a HUB gene,the expression of CCR2 was significantly up-regulated in eDN;immunohistochemistry and RT-qPCR showed that the relative expression of CCR2 in e DN group was significantly higher than that in NC group(all P<0.05).Conclusion KEGG analysis of functional enrichment mainly shows that the inflammatory pathway is activated,and the expression of CCR2 is significantly up-regulated in eDN kidney tissue,suggesting that it may play an important role in the occurrence and development of eDN.

关 键 词：糖尿病肾病 生物信息学 CCR2 炎症反应 

分 类 号：R587.1[医药卫生—内分泌]