炎症通路在强直性脊柱炎发病中作用的转录组学研究

doi:10.3969/j.issn.2095-9400.2019.12.004

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摘要目的：研究强直性脊柱炎（AS）的转录组学以阐释该疾病发病中涉及的关键基因和通路。方法：收集AS患者及健康对照外周血单个核细胞，提取RNA，通过高通量RNA测序的方法得到基因表达谱。采用生物信息学方法，比较AS患者及健康对照者的基因表达情况，选差异基因，并进行GO功能注释、KEGG通路富集分析、蛋白互相作用网络分析（PPI）及表型分析。并用ELISA方法在AS患者和健康对照者外周血中进一步验证通路中涉及的重要细胞因子的水平。结果：AS患者和健康对照者存在153个差异表达基因（DEGs），其中149个基因上调，4个基因下调，这些基因相互之间密切联系。通过上调基因的生物功能分析后发现，其主要与TNF信号通路、趋化因子信号传导等炎症通路相关。另外，在外周血浆中验证到，AS患者较健康对照者炎症细胞因子IL-2、IL-6、IL-10、TNF-α和IFN-γ的表达水平显著升高（P＜0.05）。结论：TNF、趋化因子信号传导等信号通路以及IL-2、IL-6、IL-10、TNF-α和IFN-γ等炎症因子与AS发病有关。

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	李辰璐
	方锦霞
	罗京
	朱小春
	王晓冰

关键词 ：强直性脊柱炎, RNA测序, 炎症

Abstract：Objective: To study the transcriptomics of ankylosing spondylitis (AS) to elucidate the key genes and pathways involved in the pathogenesis of the disease. Methods: Peripheral blood mononuclear cells from AS patients and healthy controls were collected. RNA was extracted and gene expression profiles were obtained by high-throughput RNA sequencing. Bioinformatics method was used to compare the gene expressions of AS patients and healthy controls to find differentially expressed genes (DEGs). GO function annotation was performed, and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment as well as protein interaction network (PPI) were analyzed. The levels of important cytokines involved in the pathway were further verified in the peripheral blood of AS patients and healthy controls by Enzyme-linked immunosorbent assay (ELISA). Results: We found 153 differentially expressed genes (DEGs) in AS patients and healthy controls, of which 149 genes were up-regulated and 4 genes down-regulated, and all of them were closely related to each other. The biological function of the up-regulated gene was found to be mainly related to inflammatory pathways such as TNF signaling pathway and chemokine signaling. In addition, it was confirmed in peripheral plasma that the expression levels of inflammatory cytokines IL-2, IL-6, IL-10, TNF-α and IFN-γ were significantly higher in AS patients than in healthy controls (P<0.05). Conclusion: This study reveals important inflammatory genes and signaling pathways that play a role in the pathogenesis of ankylosing spondylitis, which provides a reference for targeted anti-inflammatory therapy in AS patients.

收稿日期: 2019-05-22

基金资助:浙江省医药卫生科技计划项目（2019RC050）；温州市科技计划项目（Y20160028）。

通讯作者: 王晓冰，副主任医师，Email：gale820907@163.com。

作者简介: 李辰璐（1995-），女，浙江乐清人，硕士生。

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https://xb.wmu.edu.cn/CN/10.3969/j.issn.2095-9400.2019.12.004 或 https://xb.wmu.edu.cn/CN/Y2019/V49/I12/872

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