Discover the key genes for glomerular inflammation in patients with type Ⅱ diabetic nephropathy based on bioinformatics and network pharmacology

Objective:Network pharmacology and bioinformatics were used to analyze the key genes of kidney damage in diabetic nephropathy(DN)patients and explore the effect of expression changes of key genes.Methods:The gene chip dataset GSE96804 of glomerular transcriptome samples and healthy human samples with type Ⅱ diabetes 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 type 2 diabetic nephropathy were obtained through ontological(GO)enrichment and KEGG pathway enrichment analysis through GSEA annotation.The crosstalk between two results was analyzed by protein-protein interaction network(PPI).The human transcript 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 type 2 diabetic 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,tolllike receptor pathways,adipocycyte cytokine signaling pathways,cell adhesion pathways,and cytochemotokine pathways.It is judged to be highly related to 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 pathways for inducing inflammation in nephropathy in patients with type 2 diabetes,and CD8A,PTPRC,TCR2,CCL5,and ITGAM may be potential biomarkers for DN diagnosis.