title: Rhythmic pressure waves induce mucin5AC expression via an EGFR-mediated signaling pathway in human airway epithelial cells.
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.
authors.affiliation: Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Yuzhong District, Chongqing, China.
authors.forename: Chunyi
authors.initials: C
authors.lastname: Liu
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhou
authors.forename: Victor P
authors.initials: VP
authors.lastname: Kolosov
authors.forename: Juliy M
authors.initials: JM
authors.lastname: Perelman
mesh_terms: D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000235:genetics*; D055271:Mucin 5AC / Q000235:genetics* / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism / Q000502:physiology; D011312:Pressure; D034741:RNA, Small Interfering / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C524678:MUC5AC protein, human; D055271:Mucin 5AC; D034741:RNA, Small Interfering; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt