PCDH9影响过敏性鼻炎鼻黏膜上皮屏障功能的体外研究

doi:10.3969/j.issn.1006-7795.2022.06.011

首都医科大学学报 ›› 0, Vol. ›› Issue (): 886-892.doi: 10.3969/j.issn.1006-7795.2022.06.011

PCDH9影响过敏性鼻炎鼻黏膜上皮屏障功能的体外研究

王麒淇¹, 蓝凤¹, 王晶¹, 郝柳思琪^1,2, 李艳¹, 张罗^1,2,3,4*

1.北京市耳鼻咽喉科研究所,鼻病研究北京市重点实验室,北京100005;
2.首都医科大学附属北京同仁医院耳鼻咽喉头颈外科,北京100730;
3.首都医科大学附属北京同仁医院过敏科,北京100730;
4.中国医学科学院慢性鼻病诊疗策略研究创新单元,北京100730

收稿日期:2022-09-06 出版日期:2022-11-30 发布日期:2022-11-30
基金资助:
北京市科技新星计划(Z191100001119117),北京市科技计划首都健康保障培育研究项目(Z181100001618002),教育部长江学者创新团队(IRT13082),中国医学科学院医学与健康科技创新工程项目(2019-I2M-5-022),首都医科大学科研培育基金(自然类)项目(PYZ20111)。

The effects of PCDH9 on function of nasal epithelial barrier in vitro in allergic rhinitis

Wang Qiqi¹, Lan Feng¹, Wang Jing¹, Hao Liusiqi^1,2, Li Yan¹, Zhang Luo^1,2,3,4*

1. Beijing Institute of Otolaryngology,Beijing Key Laboratory of Nasal Diseases, Beijing 100005, China;
2. Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;
3. Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;
4. Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing 100730, China

Received:2022-09-06 Online:2022-11-30 Published:2022-11-30
Contact: ^*E-mail:dr.luozhang@139.com

摘要/Abstract

摘要： 目的本研究拟探讨原钙黏蛋白9(protocadherin 9, PCDH9)对过敏性鼻炎(allergic rhinitis,AR)鼻黏膜上皮屏障功能的影响。方法选取GEO数据库中正常人和AR患者鼻黏膜上皮细胞基因芯片数据进行差异基因和功能富集分析,筛选关键基因。收集正常对照和AR患者鼻黏膜上皮细胞,验证其表达水平。体外培养鼻黏膜上皮细胞(human nasal epithelial cells,HNEPC)和支气管上皮细胞(bronchial epithelial cells, BEAS-2B),过表达或敲除PCDH9,研究PCDH9表达水平对细胞紧密连接和Wnt通路激活水平的影响。结果 GSE118243基因芯片正常对照组和AR鼻黏膜上皮细胞转录组共4 406个差异基因,主要参与细胞黏附等生物学过程,其中PCDH9同时参与Wnt通路调控。实时荧光定量聚合酶链反应检测PCDH9在AR鼻黏膜上皮细胞中表达显著上调。PCDH9能够促进鼻黏膜上皮细胞闭锁连接蛋白-1(zonula occludens protein 1, ZO-1)基因和蛋白表达,抑制β-catenin蛋白表达水平。结论 PCDH9在AR患者鼻黏膜上皮中表达水平增加,在体外能够促进鼻黏膜上皮细胞紧密连接表达,抑制Wnt通路激活水平。

关键词: 过敏性鼻炎, 上皮屏障, 原钙黏蛋白, 紧密连接

Abstract: Objective To investigate the effect of protocadherin 9 (PCDH9) on function of nasal epithelial barrier in allergic rhinitis (AR). Methods The microarray data was downloaded from GEO dataset to analysis the nasal mucosa different expression genes between AR patients and control, and functional enrichment analysis of differentially expressed genes was performed to screen the hub genes. Further, nasal mucosa epithelial cells from AR patients and controls were collected to verify the hub gene expression level. PCDH9 was overexpressed or knocked down in human nasal epithelial cells (HNEPC) and bronchial epithelial cells (BEAS-2B) to identify the effect of PCDH9 on tight junction and Wnt pathway activation. Results There were 4 406 differentially expressed genes between nasal mucosa of AR and control group in GSE118243 datasets, which were mainly involved in cell adhesion biological processes. PCDH9 was both involved in Wnt signaling pathway and cell adhesion. The expression of PCDH9 was significantly upregulated in AR nasal epithelial cells compared with control by quantitative polymerase chain reaction (Q-PCR). It was further demonstrated in cellular study that PCDH9 enhanced ZO-1 mRNA and protein expression and inhibited β-catenin protein expression in nasal epithelial cells. Conclusion PCDH9 was increased in nasal mucosa of AR patients, which can promote the expression of tight junction and inhibit the activation level of Wnt signaling pathway in vitro.

Key words: allergic rhinitis, epithelial barrier, protocadherin, tight junction

中图分类号:

R765

王麒淇, 蓝凤, 王晶, 郝柳思琪, 李艳, 张罗. PCDH9影响过敏性鼻炎鼻黏膜上皮屏障功能的体外研究[J]. 首都医科大学学报, 0, (): 886-892.

Wang Qiqi, Lan Feng, Wang Jing, Hao Liusiqi, Li Yan, Zhang Luo. The effects of PCDH9 on function of nasal epithelial barrier in vitro in allergic rhinitis[J]. Journal of Capital Medical University, 0, (): 886-892.

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PCDH9影响过敏性鼻炎鼻黏膜上皮屏障功能的体外研究

The effects of PCDH9 on function of nasal epithelial barrier in vitro in allergic rhinitis

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