We aimed to investigate significant genes associated with diabetic nephropathy (DN), and their potential mechanisms in the process of DN pathogenesis. We downloaded the microarray data of GSE111154 from gene expression omnibus (GEO) database. First, we analyzed differentially expressed genes (DEGs) between early diabetic nephropathy (EDN) samples and nondiabetic control samples. Functional and pathway enrichment analysis was carried out. Disease-related gene sets were analyzed. Then, we constructed the protein–protein interaction (PPI) network and predicted the relation. Finally, transcriptional regulation analyses of microRNA and transcription factors were performed. Totally 554 DEGs between EDN samples and nondiabetic control samples were obtained. Enrichment analysis of disease-related gene sets showed that transforming growth factor beta 1 (TGFB1) was significantly enriched in DN. TGFB1 was involved in more pathways, such as proteoglycans in cancer, malaria, and amebiasis. Furthermore, TGFB1 had the highest degree in PPI network. In addition, TGFB1 was correlated with miR-21-5p, miR-146a-5p, and RAD21. TGFB1, miR-146a-5p, and miR-21-5p are important for DN development. Furthermore, TGFB1 may be involved in DN progression through the regulation of miR-21-5p, miR-146a-5p, and RAD21.
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