Zhao Zhengde, Fu Qining, Hu Liangzhu, Liu Yangdong
First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Vascular Surgery, South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China.
Front Physiol. 2021 Aug 4;12:621830. doi: 10.3389/fphys.2021.621830. eCollection 2021.
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. 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. 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, , and . Particularly, and 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 and were highly relevant to cell proliferation and inflammation with the low expression of . Besides, the biological processes and pathways in AV fistula with the high expression of 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 . We screened four potential signaling pathways relevant to intimal hyperplasia and identified 10 hub genes, including two core genes (i.e., and ). 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.
目的是通过生物信息学分析研究动静脉（AV）内瘘静脉段内膜增生关键基因的初步筛选及内膜增生潜在的分子机制。分析基因表达谱数据（GSE39488）以鉴定差异表达基因（DEG）。我们对DEG进行了基因本体论和京都基因与基因组百科全书通路富集分析。基因集富集分析（GSEA）用于了解潜在激活的信号通路。利用STRING数据库和Cytoscape软件构建蛋白质-蛋白质相互作用（PPI）网络。使用10个枢纽基因与4条关键信号通路的基因集之间的维恩图来获得核心基因和相关潜在通路。此外，进行GSEA以了解它们的生物学功能。本研究共筛选出185个DEG。AV内瘘中111个上调基因的主要生物学功能主要集中在细胞增殖和血管重塑，而AV内瘘中74个下调基因富集在主要与炎症相关的生物学功能中。GSEA发现了四条对内膜增生至关重要的信号通路，即丝裂原活化蛋白激酶（MAPK）、核苷酸结合寡聚化结构域样受体（NOD样）、细胞周期和转化生长因子-β（TGF-β）信号通路。共鉴定出10个枢纽基因，即 、 、 、 、 、 、 、 、 、 。特别地， 和 被鉴定为可能参与MAPK信号通路的核心基因。在AV内瘘中，生物学过程和通路主要涉及MAPK信号通路和MAPK介导的通路， 、 高表达时与细胞增殖和炎症高度相关， 低表达时也是如此。此外， 高表达时AV内瘘中的生物学过程和通路同样包括MAPK信号通路和由MAPK信号介导的通路， 低表达时主要与AV内瘘中的炎症有关。我们筛选出了四条与内膜增生相关的潜在信号通路，并鉴定出10个枢纽基因，包括两个核心基因（即 和 ）。两个核心基因可能参与MAPK信号通路，可能作为内膜增生的治疗靶点，以预防AV内瘘建立后发生狭窄。
