Abstract:

Abstract Objective: To investigate potential drugs for diabetic nephropathy (DN) using whole-genome expression profile and the Connectivity Map (CMAP). Methodology: Twenty three Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of micro-dissected glomeruli were measured using the Affymetrix human U133 plus 2.0 chip. Differentially expressed genes (DEGs) between late stage and early stage DN samples and CMAP database were used to identify potential drugs for DN using bioinformatics methods. The molecular mechanisms of the potential drugs were also investigated. Results: 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 showed that these drugs had therapeutic potential for DN. Conclusion: Using whole genome expression profiles and the CMAP database, the potential drugs for DN were rapidly predicted, and therapeutic potential was confirmed by previously published studies. Animal experiments and clinical trials are needed to confirm both the safety and efficacy of these drugs in the treatment of DN.

Key words: diabetic nephropathy, whole-genome expression profile, CMAP, drug screening