Dataset Information

Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli.

ABSTRACT:

Objective

To investigate potential drugs for diabetic nephropathy (DN) using whole-genome expression profiles and the Connectivity Map (CMAP).

Methodology

Eighteen Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of microdissected 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 the CMAP database were used to identify potential drugs for DN using bioinformatics methods.

Results

(1) A total of 1065 DEGs (FDR < 0.05 and fold change > 1.5) were found in late stage DN patients compared with early stage DN patients. (2) Piperlongumine, 15d-PGJ2 (15-delta prostaglandin J2), vorinostat, and trichostatin A were predicted to be the most promising potential drugs for DN, acting as NF-?B inhibitors, histone deacetylase inhibitors (HDACIs), PI3K pathway inhibitors, or PPAR? agonists, respectively.

Conclusion

Using whole-genome expression profiles and the CMAP database, we rapidly predicted potential DN drugs, 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.

SUBMITTER: Shi J

PROVIDER: S-EPMC4812204 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli.

Shi Jingsong J Jiang Song S Qiu Dandan D Le Weibo W Wang Xiao X Lu Yinhui Y Liu Zhihong Z

BioMed research international 20160316

<h4>Objective</h4>To investigate potential drugs for diabetic nephropathy (DN) using whole-genome expression profiles and the Connectivity Map (CMAP).<h4>Methodology</h4>Eighteen Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of microdissected 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 the CMAP database were used to ide ...[more]

PMID: 27069916

Similar Datasets

Project description:BackgroundDiabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus (DM). A growing body of research has demonstrated that the inflammatory state plays a critical role in the incidence and development of DN. Pyroptosis is a new way of programmed cell death, which has the particularity of natural immune inflammation. The inhibition of inflammatory cytokine expression and regulation of pathways related to pyroptosis may be a novel strategy for DN treatment. The aim of this study is to identify pyroptosis-related genes and potential drugs for DN.MethodsDN differentially expressed pyroptosis-related genes were identified via bioinformatic analysis Gene Expression Omnibus (GEO) dataset GSE96804. Dataset GSE30528 and GSE142025 were downloaded to verify pyroptosis-related differentially expressed genes (DEGs). Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a pyroptosis-related gene predictive model. A consensus clustering analysis was performed to identify pyroptosis-related DN subtypes. Subsequently, Gene Set Variation Analysis (GSVA), Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the differences between DN clusters. A protein-protein interaction (PPI) network was used to select hub genes and DGIdb database was utilized to screen potential therapeutic drugs/compounds targeting hub genes.ResultsA total of 24 differentially expressed pyroptosis-related genes were identified in DN. A 16 gene predictive model was conducted via LASSO regression analysis. According to the expression level of these 16 genes, DN cases were divided into two subtypes, and the subtypes are mainly associated with inflammation, activation of immune response and cell metabolism. In addition, we identified 10 hub genes among these subtypes, and predicted 65 potential DN therapeutics that target key genes.ConclusionWe identified two pyroptosis-related DN clusters and 65 potential therapeutical agents/compounds for DN, which might shed a light on the treatment of DN.

Dataset Information

Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli.

Objective

Methodology

Results

Conclusion

Publications

Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli.

Similar Datasets

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