低氧诱导鼻黏膜上皮细胞释放高迁移率族蛋白1促进上皮屏障损伤

郑静; 魏欣; 粘家斌; 姜鸿彦

doi:10.13201/j.issn.1001-1781.2017.15.009

低氧诱导鼻黏膜上皮细胞释放高迁移率族蛋白1促进上皮屏障损伤

- 海南省人民医院耳鼻咽喉头颈外科(海口, 570311)
基金项目:
国家自然科学基金（No：81200732）；广东省自然科学基金（No：S2012040006823）；广州市属高校"羊城学者"青年科研骨干培养项目（No：1201581626）；海南省重点研发项目（No：ZDYF2017115）

详细信息

通讯作者: 姜鸿彦,E-mail:hyjiangus@163.com

中图分类号: R765.4

收稿日期: 2017-04-27

High mobility group box1 contributes to hypoxia-induced barrier dysfunction of nasal epithelial cells

- Department of Otolaryngology Head and Neck Surgery, Hainan Provincial People's Hospital, Haikou, 570311, China

More Information

Corresponding author: JIANG Hongyan, E-mail: hyjiangus@163.com

Received Date: 27 April 2017

摘要

摘要: 目的：研究低氧对鼻黏膜上皮细胞释放高迁移率族蛋白1（HMGB1）的影响，并探讨HMGB1对鼻黏膜上皮屏障的调控作用。方法：取鼻中隔偏曲患者鼻黏膜上皮细胞进行原代培养，观察低氧条件下HMGB1的释放情况。用外源性HMGB1刺激鼻黏膜上皮细胞，检测细胞对异硫氰酸荧光素标记的葡聚糖4（FD4）通透性的影响；并通过Western blot检测上皮连接蛋白（ZO-1、Occcudin、Claudin-1和E-cadherin）的表达。结果：在低氧条件下，鼻黏膜上皮细胞释放HMGB1明显增多。HMGB1呈浓度和时间依赖效应显著增高上皮细胞对FD4的通透性；此外，上皮细胞紧密连接蛋白ZO-1、Occcudin和Claudin-1表达减少，提示上皮屏障功能受损。黏附连接蛋白E-cadherin表达无明显变化。结论：低氧通过促进鼻黏膜上皮细胞释放HMGB1，诱导黏膜上皮屏障损伤，可能在慢性鼻-鼻窦炎的发病中起重要作用。
- 低氧 /
- 高迁移率族蛋白1 /
- 上皮屏障 /
- 鼻窦炎
Abstract: Objective: To investigated the promotion of high mobility group box1(HMGB1) under hypoxia, and determined the regulatory role of HMGB1 on the barrier function of nasal epithelial cells.Method: Primary nasal epithelial cells(NECs) collected from patients with septal deviation were cultured at air-liquid interface. The release of HMGB1 under hypoxia was detected by ELISA. The effect of HMGB1 on fluorescein isothiocyanate-dextran 4 kDa(FD4) permeability of NECs was measured. Western blot analysis was utilized to examine the level of major junction proteins, namely E-cadherin, ZO-1, Occludin and Claudin-1.Result: The release of HMGB1 was significantly upregulated in NECs under hypoxia. Recombinant human HMGB1 increased FD4 permeability in a dose and time-dependent manner, indicating the impaired epithelial barrier function. HMGB1-mediated barrier hyperpermeability was accompanied by the selective downregulation of ZO-1, occludin and Claudin-1, but not E-cadherin.Conclusion: HMGB1 mediates hypoxia-induce barrier dysfunction of nasal epithelium, which may be a potential target for the treatment of chronic rhinosinusitis
- hypoxia /
- high mobility group box1 /
- epithelial barrier /
- chronic rhinosinusitis

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