影响人胰岛存活的关键基因及靶向保护方法探讨

李万里; 张莹莹; 张婷; 杨玉伟; 顾姗姗; 吴玲玲; 陈双琴; 陈继冰; 高宏君

doi:10.3969/j.issn.1674-7445.2023.02.014

影响人胰岛存活的关键基因及靶向保护方法探讨

doi: 10.3969/j.issn.1674-7445.2023.02.014

530001 南宁，广西中医药大学（李万里、张莹莹、杨玉伟、顾姗姗、吴玲玲）；广西中医药大学附属瑞康医院（张婷、陈双琴、陈继冰、高宏君）

基金项目:

国家自然科学基金青年科学基金 81900627

广西科技基地和人才专项桂科AD22035122

广西研究生教育创新计划项目 YCSW2022355

广西中医药大学研究生教育创新计划项目 YCXJ2021091

广西高校中青年教师科研基础能力提升项目 2020KY07044

广西中医药大学B类“高层次人才培育创新团队” 2022B008

详细信息

作者简介:

通讯作者:
高宏君，博士，主任医师，研究方向为器官移植与胰岛移植，Email：gao4056@163.com

中图分类号: R617, R335+.6
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出版历程
- 收稿日期: 2022-11-25
- 网络出版日期: 2023-03-15
- 刊出日期: 2023-03-15

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

Guangxi University of Chinese Medicine, Nanning 530001, China

More Information

Corresponding author: Gao Hongjun, Email: gao4056@163.com

摘要

摘要: 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。
- 胰岛移植 /
- 胰岛培养 /
- 胰岛保护 /
- 生物信息学 /
- 差异表达基因 /
- 细胞凋亡 /
- 炎症因子 /
- Toll样受体
Abstract: 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.
- Islet transplantation /
- Islet culture /
- Islet protection /
- Bioinformatics /
- Differentially expressed gene /
- Apoptosis /
- Inflammatory cytokine /
- Toll-like receptor

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图 1 不同干预时间段的交集基因

注：A图为不同时间段上调基因的交集；B图不同时间段下调基因的交集。

Figure 1. Intersection genes of different intervention time periods

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图 2 交集基因的GO富集结果

Figure 2. GO enrichment results for intersecting genes

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图 3 交集基因的KEGG富集结果

Figure 3. KEGG enrichment results for intersecting genes

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图 4 PPI网络图

注：A图为DEG编码蛋白的相互作用网络图；B图为前10个核心基因编码蛋白的相互作用网络图。

Figure 4. PPI network diagram

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图 5 核心基因的KEGG再富集结果

Figure 5. KEGG re-enrichment results of core genes

下载: 全尺寸图片幻灯片

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