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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/L866    most recent 90224.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Trinh, N. T. N. Articles by Brochiero, E. PubMed PubMed Citation Articles by Trinh, N. T. N. Articles by Brochiero, E.

EGF and K⁺ channel activity control normal and cystic fibrosis bronchial epithelia repair

¹Centre de recherche, Centre hospitalier de l'Université de Montréal (CR-CHUM)-Hôtel-Dieu, and ²Département de médecine and ³GÉPROM, Département de physiologie, Université de Montréal, Montréal, Québec, Canada

Submitted 12 March 2008 ; accepted in final form 25 August 2008

Severe lesions of airway epithelia are observed in cystic fibrosis (CF) patients. The regulatory mechanisms of cell migration and proliferation processes, involved in the repair of injured epithelia, then need to be better understood. A model of mechanical wounding of non-CF (NuLi) and CF (CuFi) bronchial monolayers was employed to study the repair mechanisms. We first observed that wound repair, under paracrine and autocrine EGF control, was slower (up to 33%) in CuFi than in NuLi. Furthermore, EGF receptor (EGFR) activation, following wounding, was lower in CuFi than in NuLi monolayers. Cell proliferation and migration assays indicated a similar rate of proliferation in both cell lines but with reduced (by 25%) CuFi cell migration. In addition, cell migration experiments performed in the presence of conditioned medium, collected from NuLi and CuFi wounded bronchial monolayers, suggested a defect in EGF/EGFR signaling in CF cells. We (49) recently demonstrated coupling between the EGF response and K⁺ channel function, which is crucial for EGF-stimulated alveolar repair. In CuFi cells, lower EGF/EGFR signaling was accompanied by a 40–70% reduction in K⁺ currents and KvLQT1, ATP-sensitive potassium (K_ATP), and Ca²⁺-activated K⁺ (KCa3.1) channel expression. In addition, EGF-stimulated bronchial wound healing, cell migration, and proliferation were severely decreased by K⁺ channel inhibitors. Finally, acute CFTR inhibition failed to reduce wound healing, EGF secretion, and K⁺ channel expression in NuLi. In summary, the delay in CuFi wound healing could be due to diminished EGFR signaling coupled with lower K⁺ channel function, which play a crucial role in bronchial repair.

airways; potassium channels; cystic fibrosis; wound repair