Identification of the Crucial Gene in Overflow Arteriovenous Fistula by Bioinformatics Analysis

作者全名："Zhao, Zhengde; Fu, Qining; Hu, Liangzhu; Liu, Yangdong"

作者地址："[Zhao, Zhengde; Fu, Qining; Hu, Liangzhu; Liu, Yangdong] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China; [Hu, Liangzhu; Liu, Yangdong] Shenzhen Univ, South China Hosp, Dept Vasc Surg, Hlth Sci Ctr, Shenzhen, Peoples R China"

通信作者："Fu, QN; Liu, YD (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China.; Liu, YD (corresponding author), Shenzhen Univ, South China Hosp, Dept Vasc Surg, Hlth Sci Ctr, Shenzhen, Peoples R China."

来源：FRONTIERS IN PHYSIOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000686205400001

JCR分区：Q2

影响因子：4

年份：2021

卷号：12

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：bioinformatics; overflow arteriovenous fistula; gene expression; neointimal hyperplasia; hemodialyis

摘要："Objective: The aim was to study the preliminary screening of the crucial genes in intimal hyperplasia in the venous segment of arteriovenous (AV) fistula and the underlying potential molecular mechanisms of intimal hyperplasia with bioinformatics analysis. Methods: The gene expression profile data (GSE39488) was analyzed to identify differentially expressed genes (DEGs). We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs. Gene set enrichment analysis (GSEA) was used to understand the potential activated signaling pathway. The protein-protein interaction (PPI) network was constructed with the STRING database and Cytoscape software. The Venn diagram between 10 hub genes and gene sets of 4 crucial signaling pathways was used to obtain core genes and relevant potential pathways. Furthermore, GSEAs were performed to understand their biological functions. Results: A total of 185 DEGs were screened in this study. The main biological function of the 111 upregulated genes in AV fistula primarily concentrated on cell proliferation and vascular remodeling, and the 74 downregulated genes in AV fistula were enriched in the biological function mainly relevant to inflammation. GSEA found four signaling pathways crucial for intimal hyperplasia, namely, MAPK, NOD-like, Cell Cycle, and TGF-beta signaling pathway. A total of 10 hub genes were identified, namely, EGR1, EGR2, EGR3, NR4A1, NR4A2, DUSP1, CXCR4, ATF3, CCL4, and CYR61. Particularly, DUSP1 and NR4A1 were identified as core genes that potentially participate in the MAPK signaling pathway. In AV fistula, the biological processes and pathways were primarily involved with MAPK signaling pathway and MAPK-mediated pathway with the high expression of DUSP1 and were highly relevant to cell proliferation and inflammation with the low expression of DUSP1. Besides, the biological processes and pathways in AV fistula with the high expression of NR4A1 similarly included the MAPK signaling pathway and the pathway mediated by MAPK signaling, and it was mainly involved with inflammation in AV fistula with the low expression of NR4A1. Conclusion: We screened four potential signaling pathways relevant to intimal hyperplasia and identified 10 hub genes, including two core genes (i.e., DUSP1 and NR4A1). Two core genes potentially participate in the MAPK signaling pathway and might serve as the therapeutic targets of intimal hyperplasia to prevent stenosis after AV fistula creation."

基金机构：Health and Family Planning Commission of Chongqing [2016ZDXM004]

基金资助正文：This study was supported by the Health and Family Planning Commission of Chongqing (Grant No. 2016ZDXM004).