Crucial genes associated with diabetic nephropathy explored by microarray analysis.
BACKGROUND
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.


METHODS
The 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.


RESULTS
Totally, 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.


CONCLUSIONS
The 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.
['Wang|Zhikui|Z|', 'Wang|Zhaoxia|Z|', 'Zhou|Zhongqi|Z|', 'Ren|Yueqin|Y|']
D000185:Actinin D002148:Calmodulin-Binding Proteins D009202:Cardiomyopathies D015923:Complement C1r D003173:Complement C1s D003599:Cytoskeleton D030541:Databases, Genetic D003928:Diabetic Nephropathies D015536:Down-Regulation D020869:Gene Expression Profiling D006801:Humans D039641:Integrin beta Chains D051821:Lymphoid Enhancer-Binding Factor 1 D035683:MicroRNAs D008840:Microfilament Proteins D009363:Neoplasm Proteins D020411:Oligonucleotide Array Sequence Analysis D014157:Transcription Factors D059467:Transcriptome D015854:Up-Regulation D051178:alpha Catenin
Diabetic nephropathy Differentially expressed gene Transcription factor Network MicroRNA