Bioinformatics Analysis of Gene Networks Related to Diabetic Nephropathy and Endothelial Activation

Diabetic nephropathy is characterized by progressive decline of renal function triggered by hyperglycemia. The endothelial cell activation and further adverse endothelium events are important for diabetic nephropathy development and progression. The molecular mechanisms of endothelial dysfunction in diabetes and chronic kidney diseases are widely discussed. The analysis of gene networks is a powerful approach to reveal molecular background of complex diseases. In this work, we applied the ANDSystem, a text-mining platform, to perform the reconstruction and analysis of the gene networks related to diabetic nephropathy and endothelial activation. These networks contained 685 and 115 genes/proteins respectively; 64 genes/proteins were common for both networks. Among the common genes, hormones, growth factors, cytokines, enzymes, receptors, chemokine ligands, transcription factors, adhesion molecules, microRNA126 and binding proteins were identified. The common genes were involved in different cellular cascades, inflammation, angiogenesis, and endothelial cell migration, according to the Gene Ontology enrichment analysis performed by DAVID web-resource. Analysis of the betweenness centrality values in the union of diabetic nephropathy and endothelial activation gene networks revealed that the most central participants among the common genes/proteins are IL-6, TNF, VEGF-A, MMP-9, LEP, CRP, CXCL8, CCL2, TLR4, ICAM-1. They could be the key regulators involved in the endothelial activation and diabetic nephropathy. According to the DrugBank database, there are target drugs with inhibiting activity for the IL-6, TNF, VEGFA, MMP-9, CXCL8, CCL2, TLR4, ICAM-1. These drugs could be considered as a promising therapy for diabetic nephropathy. The further research is required for deeper understanding and verification of obtained results.