摘要
目的:利用网络药理学、生物信息学分析糖尿病肾病(DN)患者造成肾损伤的关键基因以及探讨关键基因的表达变化对DN的影响。方法:从GEO数据库中检索并获取了2型糖尿病患者肾小球转录组样本与健康人肾小球转录组的基因芯片数据集GSE96804。通过R语言对标准化基因进行差异分析获得差异表达基因,同时通过基于本体论(GO)富集和KEGG通路富集分析、GSEA分析注释和获得与2型糖尿病肾病患者肾小球炎症相关的关键基因和通路,同时通过蛋白-蛋白相互作用网络(PPI)分析通路之间的串扰。使用人源转录本GSE30122进行验证,同时对交叉的差异基因利用Cytoscape排序,获取排名前十的关键基因作为Hub基因,用Nephroseq数据库探讨其对患者的影响。结果:通过基于R语言的limma包分析得1235个DGEs,GSEA-KEGG通路富集发现2型糖尿病肾病患者肾小球炎症主要影响包括外源性刺激,脂质水平的变化,免疫系统调节能力的激活,细胞趋化和分化以及肾脏的发育在内的多种生物过程,DGEs在转录因子通路、Toll样受体通路、脂肪细胞因子信号通路、细胞黏附通路、细胞趋化因子通路等富集,判断其与糖尿病肾病炎症有重要联系。通过与Neqhroseq比对,获取在肾小球具有表达差异的5个关键基因。结论:转录因子通路、Toll样受体通路、趋化因子信号传导、细胞黏附通路、脂肪细胞因子通路是2型糖尿病患者诱发肾病炎症的关键通路,同时CD8A、PTPRC、TCR2、CCL5、ITGAM可能为DN诊断的潜在生物标志物。
Objective:To analyze the key genes of kidney damage in diabetic nephropathy(DN)patients by using network pharmacology and bioinformatics and explore the effect of expression changes of key genes on DN.Methods:The gene chip dataset GSE96804 of glomerular transcriptome samples and glomerular transcriptome of healthy human patients with typeⅡdiabetes mellitus was retrieved and obtained from the GEO database.Differentially expressed genes(DEGs)were obtained by differential analysis of standardized genes by R language,and key genes and pathways related to glomerular inflammation in patients with typeⅡdiabetic nephropathy were obtained through ontological(GO)enrichment and KEGG pathway enrichment analysis,GSEA analysis annotation,and crosstalk between pathways was analyzed by protein-protein interaction network(PPI).The human tran-script GSE30122 was used for verification,and the crossover differential genes were sorted by Cytoscape to obtain the top ten key genes as Hub genes,and the Nephroseq database was used to explore their impact on patients.Results:Through the analysis of 1235 DGEs based on the limma package of R language,the GSEA-KEGG pathway enrichment found that glomerular inflammation in patients with typeⅡdiabetic nephropathy mainly affects a variety of biological processes including exogenous stimulation,changes in lipid levels,activation of immune system regulation,cell chemotaxis and differentiation,and kidney development,and DGEs are enriched in transcription factor pathways,toll-like receptor pathways,adipocycyte cytokine signaling pathways,cell ad-hesion pathways,and cytochemotokine pathways.It is judged to be an important link with diabetic nephropathy inflammation.By aligning with Neqhroseq,5 key genes with different expression in the glomeruli were obtained.Conclusion:Transcription factor pathway,Toll-like receptor pathway,chemokine signaling,cell adhesion pathway,and adipocytokine pathway are the key path-ways for inducing inflammation in nephropathy in patients with typeⅡdiabetes,and CD8A
作者
刘一卜
文敏
彭金刚
范菊娣
LIU Yi-bu;WEN Min;PENG jin-gang;FAN Ju-di(School of Pharmacy,Guizhou Medical University,Guiyang 550004,China;Engineering Technology Research Center of Chemical Synthetic Drug Development and Utilization in Guizhou Province,Guiyang 550004,China)
出处
《海南医学院学报》
2023年第20期1555-1562,共8页
Journal of Hainan Medical University
基金
贵州省卫生和计划生育委员会国家科学基金(gzwjkj2022-472)。
关键词
糖尿病肾病
网络药理学
生物信息学
炎症
生物标志物
Diabetic kidney disease
Network pharmacology
Bioinformatics
Inflammation
Biomarkers
