影响人胰岛存活的关键基因及靶向保护方法探讨

目的  探讨影响人胰岛存活的关键基因及靶向保护方法。方法  采用生物信息学方法，在基因表达综合（GEO）数据库中经过筛选比对，选择基因表达谱（GSE53454）。使用GEO2R工具筛选出24、48、72 h 3个时间段暴露于白细胞介素（IL）-1β和干扰素（IFN）-γ的人胰岛处理组（暴露组）和非暴露组之间的差异表达基因（DEG）。使用DAVID进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。通过STRING和Cytoscape应用构建蛋白质-蛋白质相互作用（PPI）网络。结果  共鉴定出69个上调的DEG和2个下调的DEG。GO分析结果显示，在生物过程中，DEG在对病毒的防御反应、炎症反应等方面富集；细胞成分中，DEG在细胞外隙、质膜外侧、细胞外区域显著富集；分子功能中，DEG在趋化因子活性、细胞因子活性方面显著富集。KEGG分析结果显示，DEG主要在细胞因子-细胞因子受体相互作用、病毒蛋白与细胞因子和细胞因子受体的相互作用等信号通路中富集。STRING分析结果选出了10个连接度较高的核心基因（STAT1、CXCL10、IRF1、IL6、CXCL9、CCL5、CXCL11、ISG15、CD274、IFIT3），均在暴露于IL-1β和IFN-γ的人胰岛中显著上调。KEGG再富集发现6个基因（STAT1、CXCL10、CXCL9、CXCL11、CCL5、IL6），主要在Toll样受体信号通路中显著富集。结论  STAT1、CXCL10、CXCL9、CXCL11、CCL5、IL6为影响人胰岛存活的关键基因，主要在Toll样受体信号通路中富集，是胰岛保护的重要靶点。

Analysis of key genes and targeted protection methods affecting the survival of human islets

Objective To identify the key genes and targeted protection methods affecting the survival of human islets. Methods Using bioinformatics method, the gene expression profile (GSE53454) was selected through screening and comparison from Gene Expression Omnibus(GEO) database. GEO2R tool was employed to screen the differentially expressed gene(DEG) between the human islets exposed (exposure group) and non-exposed (non-exposure group) to interleukin (IL)-1β and interferon (IFN)-γ for 24, 48 and 72 h, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID. Protein-protein interaction (PPI) network was constructed by STRING and Cytoscape apps. Results A total of 69 up-regulated DEGs and 2 down-regulated DEGs were identified. GO analysis showed that during the biological process, DEGs were enriched in the aspects of virus defense and inflammatory response. In cellular components, DEGs were significantly enriched in extracellular space, outside plasma membrane and extracellular regions. Regarding molecular functions, DEGs were significantly enriched in chemokine activity and cytokine activity. KEGG analysis revealed that DEGs were mainly enriched in multiple signaling pathways, such as cytokine-cytokine receptor interaction, virus protein-cytokine and cytokine-receptor interaction, etc. Ten key genes (STAT1, CXCL10, IRF1, IL6, CXCL9, CCL5, CXCL11, ISG15, CD274, IFIT3) with high connectivity were selected by STRING analysis, all of which were significantly up-regulated in human islets exposed to IL-1β and IFN-γ. Six genes (STAT1, CXCL10, CXCL9, CXCL11, CCL5, IL6) were screened by KEGG enrichment analysis, mainly in Toll-like receptor signaling pathway. Conclusions STAT1, CXCL10, CXCL9, CXCL11, CCL5 and IL6 are the key genes affecting the survival of human islets, which are mainly enriched in Toll-like receptor signaling pathway and act as important targets for islet protection.