Screening and functional analysis of differentially expressed genes in chronic glomerulonephritis by whole genome microarray

• Published in: Gene Vol. 589; no. 1; pp. 72 - 80
• Main Authors: Gao, Jia-rong, Qin, Xiu-juan, Jiang, Hui, Wang, Ting, Song, Jun-mei, Xu, Shuang-zhi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2016
• Subjects: Animals; Cell Cycle - genetics; CGN; Chronic Disease; Doxorubicin - toxicity; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Genome; Glomerulonephritis - chemically induced; Glomerulonephritis - genetics; Glomerulonephritis - metabolism; Glomerulonephritis - pathology; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Male; Metabolic Networks and Pathways - genetics; Microarray; Molecular mechanism; Oligonucleotide Array Sequence Analysis; Pathogenesis; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction; Syk Kinase - genetics; Syk Kinase - metabolism; GBMT; HSPG; Syk; Kng; Pathogenesis; H&E; Molecular mechanism; IP; GO; ICAM-1; CGN; Gene expression; Microarray; BCR; CRD; CCL6; RT-PCR; Runt-Related Transcription Factor 1; SPSS; Anxa1
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2016.05.031

Chronic glomerulonephritis (CGN) is the most common form of the glomerular disease with unclear molecular mechanisms, which related to immune-mediated inflammatory diseases. The aim of this study was to characterize differentially expressed genes in the normal and adriamycin-induced CGN rats by microarray analysis, and to determine the potential molecular mechanisms of CGN pathogenesis. For the gene expression analysis, fresh glomerular tissues from both normal and adriamycin treated rats (n=4, respectively) were collected. Total RNA was extracted and subjected to Agilent Rat 4×44 K whole genome microarray. KEGG, Gene Ontology (GO) analyze, LIMMA, String and Cytoscape software were applied to screen and analyze differentially regulated genes. In addition, the Real-time polymerase chain reaction (RT-PCR) was performed to verify the selected genes. 2334 differentially regulated genes were identified including 1294 up-regulated genes and 1040 down-regulated genes. According to the results of Generank, String and Cytoscape analyses, 27 genes may be key controlled genes in the pathogenesis of CGN, including 14 up-regulated genes (Fos, Myc, Kng1, Rac2, Pik3r1, Egr1, Icam1, Syk, Anxa1, Lgals3, Ptprc, Runx1, Itgb7, Ccl6) and 13 down-regulated genes (Aldh2, Dpyd, Mthfd1, Gldc, Ppar-α, Igf1, Pomc, Oas1a, Gsr, Acox1, Cyp1a1, Ugt2b15, Hsd3b6), which primarily contribute to biological processes such as, cell cycle, cell proliferation, inflammatory response, immune response, metabolic process, and so on. Fos and Syk were considered as potent hub genes. Global gene expression profile analysis showed that the molecular mechanism of CGN pathogenesis may be related to the promotion of cell cycle and mitosis, dysregulation of cytokine secretion and disordered inflammatory response as well as abnormal metabolism. •It was the first time to explore pathogenesis of CGN use whole genome microarray.•27 genes may be the key controlled genes in the pathogenesis of CGN.•Fos and Syk were considered as potent hub genes.•Pathogenesis of CGN may be related to cell proliferation, disordered inflammatory response, etc.