肿瘤坏死因子-α和白细胞介素-17A对骨关节炎患者成纤维样滑膜细胞作用的生物信息学分析

Bioinformatics Analysis of the Effects of TNF-αand IL-17A on Fibroblast-like Synoviocytes in Patients with Osteoarthritis

目的:利用生物信息学方法分析肿瘤坏死因子-α(TNF-α)和白细胞介素-17A(IL-17A)对骨关节炎患者成纤维样滑膜细胞的作用机制。方法:从GEO数据库中下载GSE93720基因芯片数据集,利用GEO2R筛选出差异表达基因。用DAVID 6.8在线数据库对差异表达基因进行GO分析和KEGG信号通路分析,String数据库构建蛋白质间相互网络,导入Cytoscape 3.7.1软件进行可视化编辑,筛选出网络中的核心基因,然后用MCODE插件进行子网络模块分析。结果:共筛选出差异表达基因256个,其中上调基因213个,下调基因43个。差异最显著的5个基因是C15orf48、CXCL8、CCL20、CXCL3、CXCR4。上调的差异基因GO分析主要涉及免疫反应、炎症反应、信号转导、细胞因子活性、趋化因子活性等。上调的差异基因KEGG信号通路分析主要涉及细胞因子-细胞因子受体相互作用、肿瘤坏死因子信号通路、趋化因子信号通路等。结论:利用生物信息学方法分析TNF-α和IL-17A诱导的骨关节炎成纤维样滑膜细胞的基因表达谱变化,为探究骨关节炎的发病机制提供指导。

Objective:To analyze the mechanism of TNF-αand IL-17A on fibroblast-like synoviocytes in patients with osteoarthritis by bioinformatics.Methods:Microarray data set GSE93720 was downloaded from the GEO database and deferentially expressed genes were screened by GEO2R.Go analysis and KEGG signal pathway analysis of deferentially expressed genes were carried out using the online database David 6.8.The inter protein network was constructed by String database.The core genes in the network were screened out by using the software of Cytoscape 3.7.1.Then the sub network module was analyzed by plug-in MCODE.Results:A total of 256 differentially expressed genes were screened,including 213 up-regulated genes and 43 down-regulated genes.The five genes with the most significant difference were C15orf48,CXCL8,CCL20,CXCL3 and CXCR4.The GO analysis for the up-regulated differential genes mainly involved immune response,inflammatory response,signal transduction,cytokine activity and chemokine activity.The KEGG signaling pathway analysis for the up-regulated differential genes mainly involves cytokine-cytokine receptor interaction,tumor necrosis factor signaling pathway and chemokine signaling pathway.Conclusion:The analysis of the gene expression profile of fibroblast-like synoviocytes in osteoarthritis induced by TNF-αand IL-17A by bioinformatics method can provide guidance for exploring the pathogenesis of osteoarthritis.