金黄色葡萄球菌生物膜致特应性皮炎的关键基因筛选及验证

Screening and Validation of Key Genes of Staphylococcus aureus Biofilm-induced Atopic Dermatitis

目的使用生物信息学方法对金黄色葡萄球菌(Staphylococcus aureus,SA)生物膜致特应性皮炎(atopic dermatitis,AD)的关键基因进行筛选、二次探索性分析,并预测潜在治疗药物。方法从GEO数据库获得GSE32920基因芯片数据,针对SA生物膜对HaCaT细胞基因表达影响进行差异表达基因筛选、GO功能富集分析、KEGG通路富集分析、蛋白互作网络构建及hub基因筛选,筛选出的关键基因及相关通路,在GSE16161和GSE32924两个人体皮肤组织的基因芯片数据进行二次探索性分析。此外,使用Connectivity Map(CMap)平台进行治疗药物的预测。结果本研究共筛选出SA生物膜对HaCaT细胞基因表达影响的差异表达基因共754个,其中显著上调404个、显著下调350个。GO功能富集分析、KEGG通路富集分析发现,差异表达基因功能主要富集于炎症反应、所参与的信号通路主要富集于IL-17信号通路、TNF信号通路等炎症通路。蛋白互作网络构建、hub基因筛选以及在两个人体数据集的二次探索性分析,最终确定了3个潜在关键靶点基因为:MMP1、CXCL1以及EGR1。CMap平台预测出evodiamine等14种小分子化合物可能成为SA生物膜皮肤感染致AD的潜在药物。结论炎症通路和MMP1、CXCL1、EGR1三个潜在关键基因,可能是SA生物膜致AD发病的关键因素,预测的小分子化合物为后续药物研究提供线索。

Objective To identify and explore key genes of Staphylococcus aureus(SA)biofilm-induced atopic dermatitis(AD)by bioinformatics method,and to predict potential therapeutic drugs.Methods The GSE32920 gene chip data were obtained from GEO database.Focusing on the effect of SA biofilm on gene expression in HaCaT cells,differentially expressed genes screening,GO functional enrichment analysis,KEGG pathway enrichment analysis,protein interaction network analysis and hub gene analysis were conducted.The key genes and related pathways were screened.The gene chip data of two human skin tissues GSE16161 and GSE32924 were used for secondary exploratory analysis.In addition,the Connectivity Map(CMap)platform was used to predict therapeutic agents.Results A total of 754 differentially expressed genes of SA biofilm affecting HaCaT cells were screened in this study,among which 404 were up-regulated and 350 were down-regulated.The GO functional enrichment analysis and KEGG pathway enrichment analysis showed that the functions of differentially expressed genes were mainly enriched in inflammatory response,and the signaling pathways involved were mainly enriched in inflammatory pathways,including IL-17,TNF signaling pathway,etc.Protein interaction network,hub gene screening and secondary exploratory analysis in two human datasets finally found three key target genes:MMP1,CXCL1,and EGR1.The CMap platform predicted that 14 small-molecule compounds such as evodiamine could be potential drugs for AD caused by SA biofilm on skin.Conclusion The inflammatory pathway and the three key genes,MMP1,CXCL1 and EGR1,may be the potential key factors in the pathogenesis of AD caused by SA biofilm.The predicted small molecular compounds provided insights for subsequent drug research.