The Study Of The Potential Drugs For Diabetic Nephropathy By Using The Whole Genome Expression Profile Of Glomerular

Objective:To investigate potential drugs for diabetic nephropathy(DN)by using the whole genome expression profile and the Connectivity Map(CMAP)Methods:Twenty nine Chinese Han DN patients and 6 normal control were selected in this study.The glomeruli were micro-dissected.The Affymetrix human U133 plus 2.0 chip were used to detect the whole genome gene expression profile of the glomeruli.The differentially expressed genes(DEGs)between the late and the early groups and CMAP were used to seek the potential drugs for DN by means of the bioinformatics methods.The molecular mechanisms of the potential drugs were also investigated.Results:(1)100 DEGs(FDR<0.05,fold change>1.5)were found in the early stage DN patients compared with the normal control,while 1602 DEGs were found in the late stage DN patients compared with the normal control.We performed gene enrichment analysis with annotation libraries of the gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)for 1194 DEGs found in the late stage DN patients compared with the early stage DN patients.The enriched GO terms are Response to stimulus,Single-organism process,Immune system process,Signaling and cell communication et al.The enriched KEGG pathways are ECM-receptor interaction,Focal adhesion,Complement and coagulation cascades,Cytokine-cytokine receptor interaction and PI3K-Akt signaling pathway et al.(2)Parthenolide,piperlongumine,15d-PGJ2 and LY-294002 were predicted to maximally reverse the disease-associated expression of genes in glomerular of DN patients.Additional literature analysis of published researches shows that these drugs have therapeutic potential for DN,acting as NF-κB inhibitors,histone deacetylase inhibitors(HDACIs),PI3K pathway inhibitors or PPARy agonists et al.Conclusions:Using the whole genome expression profile and CMAP,we rapidly predicted potential drugs for DN,and the therapeutic potential were confirmed by published researches.Animal experiments and clinical trials are needed to confirm both the safety and effectiveness of these drugs.