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



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.



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.



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.
Department of Nephrology, Linyi People's Hospital, No.27 Jiefang Road, Lanshan District, Linyi, Shandong, 276003, China.
Zhikui
Z
Wang
Department of Nephrology, Linyi People's Hospital, No.27 Jiefang Road, Lanshan District, Linyi, Shandong, 276003, China. zhaoxiazhzhh@163.com.
Zhaoxia
Z
Wang
Department of Nephrology, Linyi People's Hospital, No.27 Jiefang Road, Lanshan District, Linyi, Shandong, 276003, China.
Zhongqi
Z
Zhou
Department of Nephrology, Linyi People's Hospital, No.27 Jiefang Road, Lanshan District, Linyi, Shandong, 276003, China.
Yueqin
Y
Ren
D000185:Actinin / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D009202:Cardiomyopathies / Q000235:genetics; D015923:Complement C1r / Q000235:genetics; D003173:Complement C1s / Q000235:genetics; D003599:Cytoskeleton / Q000235:genetics; D030541:Databases, Genetic; D003928:Diabetic Nephropathies / Q000235:genetics*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D014157:Transcription Factors / Q000235:genetics*; D059467:Transcriptome; D015854:Up-Regulation; D051178:alpha Catenin / Q000235:genetics
C111453:ACTN4 protein, human; C000625216:CALD1 protein, human; C495273:CTNNA1 protein, human; D002148:Calmodulin-Binding Proteins; C000599263:ITGB5 protein, human; D039641:Integrin beta Chains; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C550416:MIRN33a microRNA, human; C486778:MTSS1 protein, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; D051178:alpha Catenin; D000185:Actinin; D015923:Complement C1r; D003173:Complement C1s
Diabetic nephropathy; Differentially expressed gene; MicroRNA; Network; Transcription factor