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

节律性压力波通过 EGFR 介导的信号通路诱导人类气道上皮细胞中 mucin5AC 的表达

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作者:Chunyi Liu, Qi Li, Xiangdong Zhou, Victor P Kolosov, Juliy M Perelman

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.

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