title: Cortactin mediates elevated shear stress-induced mucin hypersecretion via actin polymerization in human airway epithelial cells.
abstract: Mucus hypersecretion is a remarkable pathophysiological manifestation in airway obstructive diseases. These diseases are usually accompanied with elevated shear stress due to bronchoconstriction. Previous studies have reported that shear stress induces mucin5AC (MUC5AC) secretion via actin polymerization in cultured nasal epithelial cells. Furthermore, it is well known that cortactin, an actin binding protein, is a central mediator of actin polymerization. Therefore, we hypothesized that cortactin participates in MUC5AC hypersecretion induced by elevated shear stress via actin polymerization in cultured human airway epithelial cells. Compared with the relevant control groups, Src phosphorylation, cortactin phosphorylation, actin polymerization and MUC5AC secretion were significantly increased after exposure to elevated shear stress. Similar effects were found when pretreating the cells with jasplakinolide, and transfecting with wild-type cortactin. However, these effects were significantly attenuated by pretreating with Src inhibitor, cytochalasin D or transfecting cells with the specific small interfering RNA of cortactin. Collectively, these results suggest that elevated shear stress induces MUC5AC hypersecretion via tyrosine-phosphorylated cortactin-associated actin polymerization in cultured human airway epithelial cells.
authors.affiliation: Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing 400010, China. Electronic address: hczx-lcy@163.com.
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: D000199:Actins / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D051356:Cortactin / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D055271:Mucin 5AC / Q000378:metabolism*; D010766:Phosphorylation; D058105:Polymerization; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D013314:Stress, Mechanical; D014162:Transfection
chemical_list: D000199:Actins; C495868:CTTN protein, human; D051356:Cortactin; C524678:MUC5AC protein, human; D055271:Mucin 5AC
keywords: Actin polymerization; Airway obstructive diseases; Cortactin; Mucin5AC; Shear stress