Investigation of hub genes involved in diabetic nephropathy using biological informatics methods
ANNALS OF TRANSLATIONAL MEDICINE
Authors: Li, Zhanting; Liu, Jianxin; Wang, Weiwei; Zhao, Yunchun; Yang, Dengfeng; Geng, Xiaodong
Abstract
Background: The aim of this study was to find genes with significantly aberrant expression in diabetic nephropathy (DINT) and determine their underlying mechanisms. Methods: GSE30528 and GSE1009 were obtained by querying the Gene Expression Omnibus (GEO) database. The difference in target gene expression between normal renal tissues and kidney tissues in patients with DN was screened by using the GEO2R tool. Using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, differentially expressed genes (DEGs) were analysed by Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then, the protein-protein interactions (PPIs) of DEGs were analyzed by Cytoscape with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the hub genes in this PPI network were recognized by centrality analysis. Results: There were 110 genes with significant expression differences between normal and DN tissues. The differences in gene expression involved many functions and expression pathways, such as the formation of the extracellular matrix and the construction of the extracellular domain. The correlation analysis and subgroup analysis of 14 hub genes and the clinical characteristics of DN showed that CTGF, ALB, PDPN, FLT1, IGF1, WT1, GJA1, IGFBP2, FGF9, BMP2, FGF1, BMP7, VEGFA, and TGFBR3 may be involved in the progression of DN. Conclusions: We confirmed the differentially expressed hub genes and other genes which may be the novel biomarker and target candidates in DNT.
Association of vascular endothelial growth factor A polymorphisms and aberrant expression of connexin 43 and VEGFA with idiopathic recurrent spontaneous miscarriage
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
Authors: Sajjadi, Maryam S.; Ghandil, Pegah; Shahbazian, Nahid; Saberi, Alihossein
Abstract
Aim Idiopathic recurrent spontaneous miscarriage (IRSM) is one of the pregnancy outcomes that affects 1-2% of women trying to conceive. Specific genotype or aberrant expression of vascular endothelial growth factor A (VEGFA) and connexin 43 (Cx43) as two important genes for embryonic development are deemed to increase the risk of IRSM. Methods To investigate any possible association of VEGFA polymorphisms and aberrant expression of Cx43 and VEGFA with IRSM, we carried out a case-control study including embryo chorionic villus tissues of 100 pregnant women with IRSM and 100 embryo chorionic villus tissues of healthy pregnant women without history of miscarriage. Restriction fragment length polymorphism was used for genotyping of rs699947 (-2578C/A) and rs2010963 (-634G/C) polymorphisms in VEGFA. Besides, quantitative real-time PCR was performed for VEGFA and Cx43 expression analysis. Results The results showed that the frequency of -634G/C and C/C genotypes was significantly higher in aborted fetuses (P = 0.001 and P < 0.001, respectively) compared to the control group's. However, the frequency of -2578C/A genotypes was not significantly different between the cases and controls. Moreover, a significant higher expression of VEGF (P = 0.0005) and Cx43 (P = 0.0011) was observed in chorionic villus tissues of women with IRSM. Conclusion The finding demonstrated that IRSM frequency may depend on GC and CC genotypes of rs2010963 VEGF polymorphism and expression level of VEGF and Cx43 in IRSM patients was increased.