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节律性压力波通过 EGFR 介导的信号通路诱导人呼吸道上皮细胞黏蛋白 5AC 的表达。

Rhythmic pressure waves induce mucin5AC expression via an EGFR-mediated signaling pathway in human airway epithelial cells.

机构信息

Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Yuzhong District, Chongqing, China.

出版信息

DNA Cell Biol. 2013 Aug;32(8):423-9. doi: 10.1089/dna.2013.2079. Epub 2013 Jun 15.

Abstract

Rhythmic pressure waves (RPW), mimicking the mechanical forces generated during normal breathing, play a key role in airway surface liquid (ASL) homeostasis. As a major component of ASL, we speculated that the mucin5AC (MUC5AC) expression must also be regulated by RPW. However, fewer researches have focused on this question. Therefore, our aim was to test the effect and mechanism of RPW on MUC5AC expression in cultured human bronchial epithelial cells. Compared with the relevant controls, the transcriptional level of MUC5AC and the protein expressions of MUC5AC, the phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-related kinase (p-ERK), and phospho-Akt (p-Akt) were all significantly increased after mechanical stimulation. However, this effect could be significantly attenuated by transfecting with EGFR-siRNA. Similarly, pretreating with the inhibitor of ERK or phosphatidylinositol 3-kinases (PI3K)/Akt separately or jointly also significantly reduced MUC5AC expression. Collectively, these results indicate that RPW modulate MUC5AC expression via the EGFR-PI3K-Akt/ERK-signaling pathway in human bronchial epithelial cells.

摘要

节奏性压力波(RPW)模拟正常呼吸过程中产生的机械力,在气道表面液体(ASL)动态平衡中发挥关键作用。作为 ASL 的主要成分之一,我们推测黏蛋白 5AC(MUC5AC)的表达也必须受到 RPW 的调节。然而,目前针对这一问题的研究较少。因此,我们的目的是测试 RPW 对培养的人支气管上皮细胞中 MUC5AC 表达的影响及其机制。与相关对照相比,机械刺激后,MUC5AC 的转录水平以及 MUC5AC、磷酸化表皮生长因子受体(p-EGFR)、磷酸化细胞外信号调节激酶(p-ERK)和磷酸化 Akt(p-Akt)的蛋白表达均显著增加。然而,用 EGFR-siRNA 转染可显著减弱这种作用。同样,单独或联合使用 ERK 抑制剂或磷脂酰肌醇 3-激酶(PI3K)/Akt 抑制剂也可显著降低 MUC5AC 的表达。综上所述,这些结果表明,RPW 通过人支气管上皮细胞中的 EGFR-PI3K-Akt/ERK 信号通路来调节 MUC5AC 的表达。

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