Abstract
BackgroundThis study sought to investigate crucial genes correlated with diabetic nephropathy (DN), and their potential functions, which might contribute to a better understanding of DN pathogenesis.MethodsThe microarray dataset GSE1009 was downloaded from Gene Expression Omnibus, including 3 diabetic glomeruli samples and 3 healthy glomeruli samples. The differentially expressed genes (DEGs) were identified by LIMMA package. Their potential functions were then analyzed by the GO and KEGG pathway enrichment analyses using the DAVID database. Furthermore, miRNAs and transcription factors (TFs) regulating DEGs were predicted by the GeneCoDis tool, and miRNA-DEG-TF regulatory network was visualized by Cytoscape. Additionally, the expression of DEGs was validated using another microarray dataset GSE30528.ResultsTotally, 14 up-regulated DEGs and 430 down-regulated ones were identified. Some DEGs (e.g. MTSS1, CALD1 and ACTN4) were markedly relative to cytoskeleton organization. Besides, some other ones were correlated with arrhythmogenic right ventricular cardiomyopathy (e.g. ACTN4, CTNNA1 and ITGB5), as well as complement and coagulation cascades (e.g. C1R and C1S). Furthermore, a series of miRNAs and TFs modulating DEGs were identified. The transcription factor LEF1 regulated the majority of DEGs, such as ITGB5, CALD1 and C1S. Hsa-miR-33a modulated 28 genes, such as C1S. Additionally, 143 DEGs (one upregulated gene and 142 downregulated genes) were also differentially expressed in another dataset GSE30528.ConclusionsThe genes involved in cytoskeleton organization, cardiomyopathy, as well as complement and coagulation cascades may be closely implicated in the progression of DN, via the regulation of miRNAs and TFs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0343-2) contains supplementary material, which is available to authorized users.
Highlights
This study sought to investigate crucial genes correlated with diabetic nephropathy (DN), and their potential functions, which might contribute to a better understanding of DN pathogenesis
Diabetic nephropathy (DN) is a complication correlated with both type 1 and type 2 diabetes and is characterized by glomerulosclerosis due to accumulation of extracellular matrix [1]
Identification of differentially expressed genes (DEGs) Based on the cut-off criteria, a set of 444 genes were identified to be differentially expressed in the diabetic glomeruli samples, including 14 up-regulated and 430 down-regulated ones, compared with the controls (Additional file 1)
Summary
This study sought to investigate crucial genes correlated with diabetic nephropathy (DN), and their potential functions, which might contribute to a better understanding of DN pathogenesis. Diabetic nephropathy (DN) is a complication correlated with both type 1 and type 2 diabetes and is characterized by glomerulosclerosis due to accumulation of extracellular matrix [1]. Despite great attention from both clinicians and basic scientists, the morbidity of end-stage renal disease and glomerulosclerosis in diabetic patients is increasing dramatically [2]. The mammalian target of rapamycin (mTOR) complex 1 activation has a key role in podocyte dysfunction in diabetic mice [3, 4]. The pathways which the differentially expressed genes (DEGs) participate in and regulators that target these genes remain unknown
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