变应性鼻炎特异性病毒应答相关基因的生物信息学分析
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1.复旦大学附属眼耳鼻喉科医院耳鼻咽喉科;2.中山大学附属第一医院耳鼻咽喉科医院 广州市耳鼻咽喉科学重点实验室

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Identification of the AR-specific Gene Responding to dsRNA in Nasal Epithelium
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Department of Otolaryngology, Head and Neck Surgery, Affiliated Eye and ENT Hospital, Fudan University

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    【目的】变应性鼻炎(Allergic rhinitis,AR)患者感染鼻病毒(rhinovirus,RV)后病情及气道炎症加重,但其分子机制尚未完全阐明。【方法】本研究通过生物信息学方法分析双链RNA(dsRNA)刺激后AR鼻黏膜上皮细胞中特异的基因表达特征。基于GEO数据库的GSE51392数据集,利用R语言的Limma函数筛选出dsRNA刺激后AR上皮细胞特异性差异表达基因(DEGs)。通过GO和KEGG进行通路富集分析,以确定这些基因参与的生物学过程及功能。此外,通过STRING数据库构建蛋白质相互作用(PPI)网络,并使用Cytoscape寻找AR特异性的hub基因和集簇。【结果】共筛选出545个上调和400个下调的AR特异性DEGs,包括上调基因PPBP/CXCL7和下调基因IL20、BLNK、CEBPD、LY96。通过GO和KEGG分析,我们发现dsRNA刺激后AR与HC上皮相比具有不同的功能和信号通路。此外,AR特异性的DEGs构建了由791个节点和603条连线组成的PPI网络。并利用MCODE从该PPI网络中筛选出PPBP/CXCL7等16个hub基因和5个重要集簇。【结论】本研究通过生物信息学对数据进行挖掘并筛选出dsRNA刺激后AR特异性病毒应答相关基因,提示上调的hub基因CXCL7以及下调的IL20、BLNK、CEBPD和LY96可能是RV诱发AR加重的重要因素。为下一步的研究提供参考。

    Abstract:

    Objectives: Allergic rhinitis (AR) patients infected with rhinovirus (RV) exhibit severer condition and more airway inflammation. However, the mechanisms of airway inflammation exacerbated by RV are still largely unknown. Methods: Bioinformatic tools were used to identify the differentially expressed genes (DEGs) specific in AR nasal epithelium responding to dsRNA based on the GSE51392 dataset retrieved from the Gene Expression Omnibus (GEO) database. DEGs were enriched by Gene ontology (GO) and the Kyoto encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. In addition, protein-protein interaction (PPI) network was constructed to find the key genes and modules specific in AR. Results: From GSE51392 dataset, we identified 545 up-regulated and 400 down-regulated AR-specific genes in nasal epithelium responding to dsRNA, including up-regulated PPBP/CXCL7 and down-regulated IL20, BLNK, CEBPD, LY96. After GO and KEGG analyses, we found different functions and signaling pathways in nasal epithelium of AR compared to HC. In addition, the PPI network of DEGs was constructed, which was composed of 791 nodes and 603 edges. 16 genes with high degrees, including PPBP/CXCL7, were identified as hub genes, and five important modules were selected from PPI network using MCODE. Conclusion: Our data suggested that up-regulated PPBP/CXCL7 and down-regulated IL20, BLNK, CEBPD, LY96 may be important contributors to RV induced AR exacerbation. We also found different functions and signaling pathways in nasal epithelium of AR compared to HC. These results may help to understand the underlying mechanisms linking RV infection to AR exacerbation.

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  • 收稿日期:2021-12-01
  • 最后修改日期:2022-01-10
  • 录用日期:2022-01-11
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