Bioinformatics Identification of Vascular Endothelial Growth Factors as a Therapeutic Target for Diabetic Nephropathy

Background: Vascular endothelial growth factor (VEGF) functions are different in different tissues and organs and different functional states. VEGF is highly expressed in early stage diabetic nephropathy (DN) and in turn, lowly expressed in late stage DN. However, their roles in renal progression in advanced diabetes remain unclear. The purpose of this study was to determine the relationship between low VEGF expression and the pathogenesis and prognosis of advanced DN. Methods: Our study found significant differences in VEGF gene expression using data from the Gene Expression Omnibus (GEO) database based on renal tissue samples of DN and normal people. Then, we performed several bioinformatics analyses to determine differentially expressed genes, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, Gene-Set Enrichment Analysis (GSEA), and immune infiltration analysis on DN samples to obtain information on VEGF genes. Finally, we constructed protein-protein interaction networks, and screened hub-genes to refine our results further. Results: We found 180 differentially expressed genes through our bioinformatics analysis. They were also enriched in inflammatory response, cell differentiation, cell chemotaxis, proliferation, and apoptosis pathways. We found eight hub-genes by PPI network analysis. Together with VEGF, they may play a key role in regulating the development of DN. Conclusion: Our study revealed the molecular mechanism of DN pathogenesis and provides evidence that a decrease in VEGF expression in moderate-to-late DN could be related to its clinical prognosis. VEGF may be expected to become a new target for DN therapy based on this research.