鞭毛蛋白诱导表达差异基因的分析

Functional analysis of DGEs induced by flagellin

试验旨在分析鞭毛蛋白刺激机体基因表达谱的特征,揭示鞭毛蛋白佐剂的作用机制。从GEO数据库筛选目标微阵列GSE46421和GSE72016及其差异表达基因(DEGs),经DAVID分析DEGs参与的GO功能注释和KEGG信号通路、String构建DEGs的蛋白质-蛋白质相互作用(PPI)网络、Cytoscape可视化PPI网络并筛选高连通度的PPI子模块和hub基因。结果显示,共筛选出182个DEGs,包含上调基因161个、下调基因121个。DEGs参与GO生物过程主要有信号转导、免疫应答、炎症反应、细胞凋亡等,参与分子功能包含激酶激活、受体结合、细胞因子激活、膜信号转导。DEGs参与KEGG通路涵盖细胞因子-细胞因子受体相互作用、TNF信号通路、NF-κB信号通路、Toll样受体信号通路、NOD样受体信号通路等免疫相关途径。分析DEGs的PPI网络发现,2个重要的PPI子模块和10个关键基因(IL-10、IL-6、CCL2、CXCL2、NFKBIA、MyD88等)。研究表明,鞭毛蛋白通过识别TLR5和NOD样受体,触发MyD88依赖性和MyD88非依赖性途径发出信号,激活转录因子NF-κB,这些信号通过级联反应激活机体免疫系统、诱导机体产生多种细胞因子和趋化因子,发挥佐剂效应。

The study was to analyze the characteristics of gene expression profiles stimulated by flagellin adjuvants,to reveal potential mechanism of flagellin adjuvant.The target microarray datasets GSE46421 and GSE72016 were screened from GEO database,and DEGs of two datasets were analyzed.The GO biological functions and KEGG signaling pathway involved in DEGs were analyzed by DAVID,PPI network of DEGs was constructed by String and visualized by Cytoscape.PPI network was visualized by Cytoscape,PPI sub-modules and hub genes with high connectivity were screened.The results showed that a total of 182 DEGs were screened,including 161 up-regulated genes and 121 downregulated genes.DEGs involved in GO biological processes mainly included signal transduction,immune response,inflammatory response,apoptosis,etc.,molecular functions include kinase activation,receptor binding,cytokine activation and membrane signal transduction.The DEGs involved in KEGG pathways included cytokine-cytokine receptor interaction,TNF signaling pathway,NF-κB signaling pathway,Toll-like receptor signaling pathway,NOD-like receptor signaling pathway and other immune-related pathways.Analysis of the PPI network of DEGs revealed two important PPI sub-modules and ten key genes(IL-10,IL-6,CCL2,CXCL2,NFKBIA,MyD88,etc.).The study indicates that flagellin triggers MyD88-dependent and MyD88-independent pathways to signal and activate transcription factor NF-κB by recognizing TLR5 and NOD-like receptors.These signals activate the immune system and induce the production of various cytokines and chemokines in body through a cascade reaction,which plays an adjuvant effect.