title: Caveolin-1 aggravates cigarette smoke extract-induced MUC5AC secretion in human airway epithelial cells.
abstract: Airway mucus hypersecretion is a major pathological characteristic of chronic obstructive pulmonary disease (COPD), and cigarette smoke is highly implicated in mucus secretion and the development of COPD. Cigarette smoke reportedly induces mucin overproduction through the epidermal growth factor receptor (EGFR) in the airway epithelium; however, the underlying mechanisms responsible for the activation of EGFR remain unknown. Caveolin-1, a component protein in the cytomembrane, reportedly regulates airway inflammation and lung injury. In this study, we aimed to determine whether caveolin-1 modulates mucin hyperproduction induced by cigarette smoke. Our results revealed that cigarette smoke extract (CSE) significantly increased MUC5AC production, as well as the levels of phosphorylated EGFR (p-EGFR) and phosphorylated Akt (p-Akt) in human bronchial epithelial cells (16HBE cells), as shown by ELISA, RT-PCR and western blot analysis. These effects were prevented by treatment with EGFR inhibitor (AG1478) and phosphatidylinostol-3-kinase (PI3K) inhibitor (LY294002). We also found that the overexpression of caveolin-1 enhanced the expression of MUC5AC, p-EGFR and p-Akt induced by CSE. Conversely, the downregulation of caveolin-1 by siRNA against caveolin-1 inhibited the expression of MUC5AC, p-EGFR and p-Akt. Taken together, our data suggest that caveolin-1 enhances CSE-induced MUC5AC hypersecretion through the EGFR/PI3K/Akt signaling pathway.
authors.affiliation: Department of Gerontology and Respirology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Gerontology and Respirology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Gerontology and Respirology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Gerontology and Respirology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Gerontology and Respirology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Chengping
authors.initials: C
authors.lastname: Hu
mesh_terms: D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects*
chemical_list: D051242:Caveolin 1; D055271:Mucin 5AC; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt