[1]乐艳青,董航明,王燕红,等.表皮生长因子受体参与屋尘螨诱导的气道上皮屏障破坏的机制[J].南方医科大学学报,2017,(06):737.
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表皮生长因子受体参与屋尘螨诱导的气道上皮屏障破坏的机制()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2017年06期
页码:
737
栏目:
出版日期:
2017-06-20

文章信息/Info

Title:
Role of epidermal growth factor receptor in house dust mite-induced airway epithelial barrier dysfunction
作者:
乐艳青董航明王燕红赵海金蔡绍曦
关键词:
表皮生长因子受体肌动蛋白应力纤维屋尘螨气道上皮屏障破坏
Keywords:
epidermal growth factor receptor F-actin house dust mite airway epithelia barrier dysfunction
摘要:
目的探讨屋尘螨(HDM)对肌动蛋白应力纤维(F-actin)重新排布的影响及表皮生长因子受体(EGFR)相关信号通路在其 中的作用。方法选取正常人支气管上皮细胞系16HBE细胞为研究对象,以HDM刺激细胞,予EGFR抑制剂AG-1478进行预 处理,实验分为4组:Control组,AG-1478组,HDM组,AG-1478+HDM组,应用Western blotting检测HDM对磷酸化(p-)EGFR、 F-actin及粘附连接蛋白E-cadherin和β-catenin表达的影响,应用免疫荧光技术观察F-actin、E-cadherin及β-catenin的分布变化, 并测量16HBE细胞层的跨上皮电阻(TER)值和右旋糖苷(FITC-DX)的透过率。结果HDM刺激细胞10 min时,p-EGFR表达 明显增多(P<0.05),E-cadherin(P>0.05)及β-catenin(P>0.05)蛋白表达无明显改变,免疫荧光示HDM刺激后E-cadherin 及 β-catenin均发生分布异常,由胞膜向胞浆弥散。HDM组TER值(70.00±4.33)%显著下降,FITC-DX透过率(115.98±4.34)%明显 增加,加入EGFR抑制剂后E-cadherin和β-catenin的分布异常及TER值(90.00±3.75)%、FITC-DX(101.10±2.10)%透过率均明显 改善。HDM刺激后促进F-actin表达增多并出现重新排布,而EGFR抑制剂可明显抑制这一过程(P<0.05)。结论表皮生长因 子受体相关信号通路参与了屋尘螨介导肌动蛋白应力纤维的重新排布,并导致气道上皮屏障破坏。
Abstract:
Objective To investigate the role of epidermal growth factor receptor (EGFR) signaling pathway in bronchial epithelial actin stress fiber (F-actin) rearrangement induced by house dust mite (HDM). Methods Normal human bronchial epithelial cells (16HBE) were stimulated with HDM with or without pretreatment with AG-1478, an EGFR inhibitor. The levels of phospho(p)-EGFR, F-actin, E-cadherin and β-catenin in the cell cultures were detected with Western blotting. The localizations of F-actin, E-cadherin and β-catenin in the bronchial epithelial cells were determined with immunofluorescence assay, and the transmembrane electrical resistance (TER) and FITC-dextran flux (FITC-DX) in the cells were measured to assess the barrier function of the bronchial epithelia. Results HDM stimulation of the cells for 10 min resulted in significantly increased p-EGFR expression (P<0.05) without causing obvious changes in the expression of E-cadherin (P>0.05) or β-catenin (P>0.05). Immunofluorescence assay revealed delocalization of E-cadherin and β-catenin in HDM-treated 16HBE cells, shown by their diffusion from the cell membrane to the cytoplasm. In HDM-treated cells, the TER was significantly decreased to (70.00±4.33)% and the FITC-DX was significantly increased to (115.98±4.34)%; Inhibition of EGFR reversed the delocalization of E-cadherin and β-catenin, improved the TER to (90.00 ± 3.75)% and lowered the FITC-DX to (101.10 ± 2.10)%. HDM induced increased expression and rearrangement of F-actin, which was obviously inhibited by pretreatment of the cells with AG-1478 (P<0.05). Conclusion EGFR signaling pathway mediates HDM-induced F-actin rearrangement in human bronchial epithelial cells to contribute to epithelial barrier dysfunction.

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更新日期/Last Update: 1900-01-01