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气道黏液高分泌的信号传导通路 被引量:10

Signaling pathway in human airway mucous hypersecretion
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摘要 目的探讨中性粒细胞弹性蛋白酶(NE)诱导气道黏蛋白(MUC)5AC基因表达的信号传导机制。方法用NE刺激A549细胞,以活性氧(ROS)清除剂DMTU、组织激肽释放酶抑制剂aprotinin和表皮生长因子受体(EGFR)酪氨酸激酶抑制剂AG1478为干预条件,用RT-PCR检测MUC5AC转录水平,用ELISA和Western blot法检测表皮生长因子(EGF)、EGFR及其磷酸化水平。结果NE刺激组MUC5AC mRNA水平显著高于对照组,同时伴有EGF浓度升高和磷酸化EGFR增加。DMTU、aprotinin和AG1478干预组MUC5AC mRNA水平与NE刺激组相比显著降低,DMTU和aprotinin干预组EGF和磷酸化EGFR也显著降低。结论NE经EGFR信号通路诱导A549细胞MUC5AC表达,其上游途径有氧化剂、组织激肽释放酶和EGF参与。 Objective To explore the upstream signal transduction pathway of neutrophil elastase (NE)-induced mucin(MUC)SAC gene expression. Methods A549 cells were either incubated with NE alone or with DMTU, aprotinin or AG1478. The level of MUC5AC mRNA was measured with RT-PCR. The activation of epidermal growth factor receptor (EGFR) and signaling were assessed by measuring the release of epidermal growth factor (EGF) and the phosphorylation of EGFR. Results NE increased MUCSAC gene expression accompanied by an increase of EGF and phosphorylated EGFR. DMTU, aprotinin and AG1478 significantly inhibited MUCSAC gene expression. DMTU and aprotinin significantly decreased the level of EGF and phosphorylated EGFR. Conclusion NE can induce MUCSAC gene expression via EGFR signalling in A549 ceils. The upper stream involves oxidants, activation of tissue kallikrein and EGF.
出处 《基础医学与临床》 CSCD 北大核心 2008年第11期1142-1145,共4页 Basic and Clinical Medicine
基金 国家自然科学基金(30770951)
关键词 弹性蛋白酶 氧化剂 表皮生长因子受体 黏液高分泌 NE oxidant EGF receptor mucus hypersecretion
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参考文献9

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二级参考文献28

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