Identification and Validation of Hub Genes and Pathways in the Stenosis of Arteriovenous Fistula

Abstract

Abstract Background and Purpose Arteriovenous fistula (AVF) is the most widely used hemodialysis vascular access in China. However, stenosis of AVF limited its use. Moreover, the mechanism of AVF stenosis is currently unknown. Therefore, the purpose of our study is to explore the mechanisms of AVF stenosis. Materials and Methods In this study, we identified differentially expressed genes (DEGs) based on Gene Expression Omnibus (GEO) dataset (GSE39488) between venous segments of overflowing of AVF and normal veins. Gene set enrichment analysis (GSEA) were performed for the functional annotation of DEGs. A protein-protein interaction (PPI) network was created to identify the hub genes of AVF stenosis. Combining the results of GSEA and PPI network analysis, along with analyses from other literatures, FOS and NR4A2 were selected as the target genes to be further investigated. Finally, we validated the bioinformatics results with reverse transcription-PCR (RT-PCR) and western blot analysis on human and rat samples, respectively. Results Six hub genes (FOS, NR4A2, EGR2, CXCR4, ATF3, and SERPINE1) were found by bioinformatics analysis. Additionally, the expression levels of mRNA and protein of FOS and NR4A2 were upregulated in both human and rat samples. Conclusions In summary, the results suggested that FOS may play an important role in AVF stenosis by activating MAPK signaling pathway, which could be a potential therapeutic target of AVF stenosis.