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

发布时间：2018-05-19 22:14

本文选题：表皮生长因子受体 + 肌动蛋白应力纤维　；参考：《南方医科大学学报》2017年06期

【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(P0.05),E-cadherin(P0.05)及β-catenin(P0.05)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(P0.05)。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 effect of HDM on the rearrangement of actin stress fiber (F-actinin) and the role of epidermal growth factor receptor (EGFR) related signaling pathway. Methods normal human bronchial epithelial cell line 16HBE cells were selected as study objects. HDM stimulated cells were pretreated with EGFR inhibitor AG-1478. The cells were divided into 4 groups: control group, AG-1478 group, HDM group, AG-1478 HDM group. Western blotting was used to detect the effect of HDM on the expression of phosphorylated p-EGFRN F-actin and adhesion protein E-cadherin and 尾 -catenin. The distribution of E-cadherin and 尾 -catenin was observed by immunofluorescence technique, and the transepithelial resistance of 16HBE cell layer was measured. The transepithelial resistance of 16HBE cell layer and the permeability of dextran FITC-DX were measured. Results the expression of p-EGFR and 尾 -catenin P0.05) in HDM stimulated cells did not change significantly after 10 min. The distribution of E-cadherin and 尾 -catenin was abnormal after HDM stimulation. The TER value (70.00 卤4.33%) decreased significantly in the group from cell membrane to cytoplasm. The transmittance of FITC-DX was significantly increased by 115.98 卤4.34%. The distribution of E-cadherin and 尾 -catenin was abnormal and the TER value was 90.00 卤3.75% in FITC-DX101.10 卤2.10%. EGFR inhibitor could significantly inhibit this process (P 0.05). Conclusion the epidermal growth factor receptor-related signaling pathway is involved in the rearrangement of actin stress fibers mediated by house dust mites and leads to the destruction of airway epithelial barrier.
【作者单位】：南方医科大学南方医院呼吸与危重症医学科慢性气道疾病实验室;
【分类号】：R562.25

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