Complement C3 as therapeutic target in diabetic nephropathy by bioinformatics analysis

Abstract Background: Various public platforms have contained extensive data for deeper bioinformatics analysis. The pathogenesis of diabetic nephropathy is always a hot topic and the underlying molecular events are not completely clear. Methods: Differential expression analysis and weighted correlation network analysis (WGCNA) were applied to screen meaningful gene in GSE30529. The combined result was used for gene ontology (GO) annotation and KEGG pathway enrichment analysis. STRING was used for protein-protein interaction (PPI) network construction and Cytoscape software was used for hub gene identification. Gene methylation profile GSE121820 and miRNA profile GSE51674 were also acquired to perform multi-omics analysis. Clinical features were obtained form Nephroseq and potential drugs were identified by CMap. Results: 345 genes were obtained form GSE30529 after differential expression analysis and WGCNA. GO analysis mainly included neutrophil activation, regulation of immune effector process, positive regulation of cytokine production and neutrophil mediated immunity. KEGG pathway analysis mostly included phagosome, complement and coagulation cascades, cell adhesion molecules and AGE-RAGE signaling pathway in diabetic complications. 16 down regulated miRNAs were obtained from GSE57674 to construct miRNA-mRNA network. Top 20 genes were discerned from PPI network and there were DNA methylation differences in 15 genes among them. Correlation analysis showed SYK, CXCL1, LYN, VWF, ANXA1, C3, HLA-E, RHOA, SERPING1, EGF and KNG1 may involved in DN. 10 small molecule compounds have been identified as potential therapeutic drugs. Conclusion: We screened 11 target genes and suggested C3 may serve as a therapeutic target in diabetic nephropathy.