转化生长因子-β1对慢性鼻-鼻窦炎伴鼻息肉上皮紧密连接屏障功能的影响

doi:10.3969/j.issn.1006-7795.2018.01.009

首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (1): 45-50.doi: 10.3969/j.issn.1006-7795.2018.01.009

• 鼻炎和鼻窦炎的基础研究 • 上一篇下一篇

转化生长因子-β1对慢性鼻-鼻窦炎伴鼻息肉上皮紧密连接屏障功能的影响

矫健¹, 张罗^1,2

1. 首都医科大学附属北京同仁医院耳鼻咽喉头颈外科北京市耳鼻咽喉科研究所教育部耳鼻咽喉头颈科学重点实验室鼻病研究北京市重点实验室, 北京 100730;
2. 首都医科大学附属北京同仁医院鼻过敏科, 北京 100730

收稿日期:2017-12-11 出版日期:2018-01-21 发布日期:2018-01-27
通讯作者: 张罗 E-mail:dr.luozhang@139.com
基金资助:
国家自然科学基金重点国际合作项目（81420108009），国家自然科学基金重点项目（81630023），教育部长江学者和创新团队发展计划（IRT13082），北京市百千万人才工程资助项目（2016），北京市自然科学基金面上项目（7172053），北京市卫生系统高层次卫生技术人才（2009-2-007，2011-3-043，2014-3-018），北京市医院管理局使命人才计划（SML20150203），北京市科技项目统筹课题（Z171100000117002），首都医科大学附属北京同仁医院科研骨干基金（2016-YJJ-GGL-007）。

Effect of transforming growth factor-β1 on tight junction barrier function in nasal epithelial cells of chronic rhinosinusitis with nasal polyps

Jiao Jian¹, Zhang Luo^1,2

1. Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing Institute of Otorhinolaryngology, Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing Key Laboratory of Nasal Diseases, Beijing 100730, China;
2. Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China

Received:2017-12-11 Online:2018-01-21 Published:2018-01-27
Supported by:
This study was supported by National Natural Science Foundation of China (81420108009,81630023),Changjiang Scholars and Innovative Research Team (IRT13082), Beijing Talent Project (2016), Natural Science Foundation of Beijing (7172053), Beijing Health Bureau Program for High Level Talents (2009-2-007, 2011-3-043, and 2014-3-018), Beijing Municipal Administration of Hospitals' Mission Plan (SML20150203), Beijing Scientific and Technological Overall Plan (Z171100000117002).

摘要/Abstract

摘要： 目的本研究旨在探讨中国汉族人群中慢性鼻窦炎伴鼻息肉（chronic rhinosinusitis with nasal polyps，CRSwNP）患者鼻腔上皮紧密连接（tight junction，TJ）屏障功能的改变以及转化生长因子-β1（transforming growth factor-β1，TGF-β1）对其调控作用。方法气液界面方法体外培养鼻息肉患者及健康对照鼻腔上皮细胞，待细胞分化完成后加入不同浓度的TGF-β1刺激上皮细胞72 h，检测上皮细胞跨膜阻力（transepithelial resistance，TER）及细胞间荧光素通透性的变化，评价上皮细胞屏障功能的改变；此外，分别应用实时荧光定量聚合酶链式反应（polymerase chain reaction，PCR）和免疫荧光技术检测紧密连接相关基因mRNA及蛋白表达的改变。结果与健康对照上皮相比，鼻息肉来源的上皮细胞TER明显降低，上皮细胞对荧光素FITC-葡聚糖（FITC-Dextran）的通透性增加，10 ng/mL TGF-β1刺激可明显降低两种上皮细胞的TER，同时增加荧光素通透性。细胞紧密连接蛋白occludin及zonula occludens（ZO）-1免疫荧光结果显示，健康对照上皮细胞间紧密连接蛋白呈现连续的线性结构，而鼻息肉上皮紧密连接蛋白表达模式呈现明显破坏，包括紧密连接线性结构分离、断裂等，而经10 ng/mL TGF-β1刺激后，无论健康对照还是鼻息肉来源的上皮细胞间紧密连接蛋白表达模式均有明显破坏。结论中国汉族鼻息肉患者的鼻腔上皮紧密连接屏障功能有明显的缺陷，而TGF-β1在诱发鼻息肉上皮屏障功能缺陷中发挥了重要的调控作用，或可作为鼻息肉治疗潜在的靶位点。

关键词: 鼻息肉, 紧密连接, 转化生长因子-β1, 调控

Abstract: Objective To investigate the epithelial tight junction (TJ) barrier integrity changes and its regulation by transforming growth factor(TGF)-β1 in Chinese patients with chronic rhinosinusitis with nasal polyps(CRSwNP).Methods Air-liquid interface(ALI) cultures were established for human nasal epithelial cells from CRSwNP patients and healthy control subjects. Differentiated cells were stimulated with different concentrations of TGF-β1, transepithelial resistance(TER) and permeability of FITC-Dextran was measured over time. Additionally, TJ protein expression was examined by using immunofluorescence and TJ mRNA expression was determined by real-time PCR.Results In comparison with control subjects, epithelial TER decreased and FITC-Dextran permeability increased in CRSwNP-derived epithelial cells along with an irregular, patchy, and decreased expression of the TJ proteins occludin and zonula occludens(ZO)-1. 10 ng/mL TGF-β1 stimulation decreased epithelial TER, increased paracellular permeability, as well as disrupted TJ protein occludin and ZO-1 expression pattern in both control and CRSwNP-derived epithelial cells.Conclusion Epithelial TJ barrier integrity was disrupted in Chinese CRSwNP patients. TGF-β1 played an important role in inducing TJ barrier defects in nasal epithelium, suggesting that it might serve as a potential therapeutic target for CRSwNP treatment.

Key words: nasal polyp, tight junction, transforming growth factor-β1, regulation

中图分类号:

R765.21

矫健, 张罗. 转化生长因子-β1对慢性鼻-鼻窦炎伴鼻息肉上皮紧密连接屏障功能的影响[J]. 首都医科大学学报, 2018, 39(1): 45-50.

Jiao Jian, Zhang Luo. Effect of transforming growth factor-β1 on tight junction barrier function in nasal epithelial cells of chronic rhinosinusitis with nasal polyps[J]. Journal of Capital Medical University, 2018, 39(1): 45-50.

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转化生长因子-β1对慢性鼻-鼻窦炎伴鼻息肉上皮紧密连接屏障功能的影响

Effect of transforming growth factor-β1 on tight junction barrier function in nasal epithelial cells of chronic rhinosinusitis with nasal polyps

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