山东大学耳鼻喉眼学报 ›› 2023, Vol. 37 ›› Issue (5): 6-15.doi: 10.6040/j.issn.1673-3770.0.2022.246
王明明,罗洋,贺少娟,张现兴,李学忠
WANG Mingming, LUO Yang, HE Shaojuan, ZHANG Xianxing, LI Xuezhong
摘要: 目的 通过生物信息学技术对慢性鼻窦炎鼻息肉基底干细胞增殖分化过程中的差异表达基因分析,为慢性鼻窦炎鼻息肉上皮屏障损伤机制及治疗提供新的思路和方向。 方法 从基因表达数据库(GEO数据库)下载慢性鼻窦炎鼻息肉基底干细胞增殖分化转录组芯片数据集,使用R软件构建加权基因共表达网络分析(WGCNA)网络,筛选与正常对照组间与疾病相关的差异表达基因,通过网络在线工具DAVID进行差异基因的基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,通过STRING数据库构建差异表达基因的蛋白相互作用网络,并应用Cytoscape中的MCODE插件对蛋白相互作用网络进行分析。最后,使用NetworkAnalys整合转录因子数据库构建核心基因的转录因子网络。 结果 研究发现基底干细胞在慢性鼻窦炎伴鼻息肉组与正常对照组间共有175个与疾病相关的差异表达基因(P<0.05,∣logFC∣>1)。GO分析和KEGG通路分析显示,这些差异基因主要富集在内肽酶活性的负调控、丝氨酸型内肽酶抑制剂活性和Wnt信号通路等。通过蛋白相互作用网络的构建及分析,筛选出IVL和SPRR2A等核心基因,它们均在基底干细胞分化过程中上调,且之间存在相互作用。GSEA分析表明,β-丙氨酸代谢可能参与慢性鼻窦炎鼻息肉的致病机制。此外,分析显示转录因子GATA2在基底干细胞分化过程中发挥关键作用。结论〓IVL、SPRR2A及GATA2转录因子可能参与了慢性鼻窦炎鼻息肉上皮屏障的损伤机制,内肽酶活性抑制可能是上皮屏障损伤的关键因素,此研究为进一步深入理解慢性鼻窦炎鼻息肉上皮屏障损伤的生物学机制及治疗提供了新思路。
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