基于生物信息学的糖尿病肾脏疾病上皮间充质转化的差异基因表达及中药预测研究

Bioinformatic-based differential expression gene expressions of epithelial mesenchymal transformation in diabetic kidney disease and prediction of traditional Chinese medicine

目的本研究基于生物信息学分析糖尿病肾脏疾病(diabetic kidney disease,DKD)患者与健康人群之间的基因芯片数据,筛选DKD上皮间充质转化的差异表达基因,从而探讨其相关发病机制,进而预测治疗DKD的潜在中药。方法从基因表达数据库下载GSE23338芯片数据,采用R语言筛选相关差异表达基因,并对差异基因进行基因本体论、京都基因与基因组百科全书数据库分析,通过STRING网站构建蛋白互作网络,运用Cytoscape软件及其插件分析得到差异基因的核心基因,将核心基因与医学本体信息检索平台相互映射,筛选治疗DKD的相关中药。结果筛选出差异基因187个,其中上调基因94个,下调基因93个。其通路富集结果主要包括肿瘤坏死因子信号通路、TGF-β信号通路、糖尿病并发症中的AGE-RAGE信号通路等。筛选得到关键核心基因主要包括FN1、TGFB1、COL1A1、SERPINE1、SNAI2、THBS1、MMP1、CDH2、JAG1、VCAM1。筛选获得相关治疗中药主要包括黄芪、车前草、积雪草、黄连、黄芩、三七等。结论本研究对差异表达基因和关键核心基因的分析促进了对DKD发病机制的理解,为在治疗DKD中药方面的新药开发提供了潜在基因靶标与研发思路。

Objective Based upon the bioinformatic analysis of gene chip data between patients with diabetic kidney disease(DKD)and normal controls,differentially expressed genes of epithelial mesenchymal transformation of DKD were screened for elucidating its pathogenesis and predicting the potential therapeutic Chinese medicine for DKD.Methods GSE23338 microarray data were downloaded from gene expression omnibus,related differentially expressed genes screened by R language and differentially expressed genes analyzed by Gene Ontology,Kyoto Encyclopedia of Genes and Genomes.Through the analysis of STRING website for establishing a network of protein-protein interaction(PPI)and Cytoscape software and its plug-ins for obtaining key core genes,core genes were mapped to Coremine Medical for screening the relevant therapeutic Chinese medicines for DKD.Results A total of 187 differential genes were screened,including 94 up-regulated and 93 down-regulated genes.Pathway enrichment results included the signaling pathways of tumor necrosis factor,TGF-βand AGE-RAGE.And key core genes included FN1,TGFB1,COL1A1,SERPINE1,SNAI2,THBS1,MMP1,CDH2,JAG1 and VCAM1.The selected TCM herbs included astragalus membranaceus,plantain,centella,coptis chinensis,scutellaria baicalensis and panax notoginseng.Conclusion Analysis of differentially expressed genes and key core genes promotes understanding of the pathogenesis of DKD and provides probable gene targets and research rationales for developing new drugs of DKD in traditional Chinese medicine.