急性肺损伤差异表达基因的生物信息学分析

Bioinformatics Analysis of Differentially Expressed Genes in Acute Lung Injury

【目的】应用生物信息学方法探讨脂多糖(LPS)诱导小鼠急性肺损伤(ALI)的相关基因,为阐明ALI的发病机制提供新思路。【方法】从NCBI(美国国立生物技术信息中心)公共数据平台GEO (Gene Expression Om-nibus)下载基因芯片数据集GSE2411、GSE17355和GSE18341,使用在线分析工具GEO2R筛选出正常肺组织与急性肺损伤组织的差异表达基因。筛选出的差异表达基因利用在线数据库DAVID进行功能注释(GO)和通路分析(KEGG),利用STRING在线数据库和Cytoscape软件进行蛋白互作网络分析并计算网络及各个节点的拓扑特性。【结果】初筛出98个差异表达基因,其中上调的93个,下调的5个。GO分析发现它们主要富集在胞外区,主要参与炎症反应、免疫反应、脂多糖反应等生物学过程,主要参与细胞因子活性、趋化因子活性、CXCR趋化因子受体结合等细胞功能;KEGG分析发现它们参与了TNF信号通路,军团病信号通路和NF-κB信号通路等。STRING在线数据库和Cytoscape软件分析发现Il6、Tlr2、Cxcl2、Ccl3、Myd88、Timp1、Tnfaip3、Fpr2、Nfkbia、Cd274等为LPS诱导小鼠ALI相关的关键基因。【结论】采用生物信息学方法能够有效分析LPS诱导小鼠ALI差异表达的基因,其中Cxcl2、Timp1和Fpr2三个基因极少或尚未研究,表明其可能是急性肺损伤发病机制的研究新靶点。

【Objective】Bioinformatics analysis was used to screen the related genes of Lipopolysaccharide(LPS)induced acute lung injury(ALI)in mice and find new clues for the mechanism of ALI.【Methods】We downloaded the gene data sets GSE2411,GSE17355 and GSE18341 from the GEO database,and screened the differentially expressed genes between normal tissues and ALI by using GEO2R analysis tools.Then,we did GO analysis and KEGG pathway analysis by the DAVID online database.Lastly,we analyzed the protein-protein interaction network by the STRING online database,and computed the network topology by the Cytoscape software.【Results】We found that 98 differentially expressed genes,of which 93 genes were up-regulated and 5 were down-regulated.GO analysis found that these genes were mainly concentrated in extracellular space,and extracellular region.Biological processes were involved in inflammation,immune response,lipopolysaccharide reaction,cellular chemotaxis,immune system processes.Molecular function was involved in cytokine activity,chemokine activity and CXCR chemokine receptor binding.KEGG pathway analysis showed that these genes were mainly involved in the TNF signal pathway,Legionnaires disease signal pathway and NF-κB signal pathway.Finally,Il6,Tlr2,Cxcl2,Ccl3,Myd88,imp1,Tnfaip3,Fpr2,Nfkbia,Cd274 were identified as the key genes associated with ALI induced by LPS.【Conclusions】The bioinformatics method can be used to analyze the differentially expressed genes of ALI induced by LPS in mice.Cxcl2,Timp1 and Fpr2 genes which have not been studied,may become new research targets for the pathogenesis of acute lung injury.