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This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: 293/4/L870    most recent 00362.2006v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Trinh, N. T. N. Articles by Brochiero, E. Search for Related Content PubMed PubMed Citation Articles by Trinh, N. T. N. Articles by Brochiero, E.

Involvement of K_ATP and KvLQT1 K⁺ channels in EGF-stimulated alveolar epithelial cell repair processes

¹Centre de Recherche, Centre Hospitalier de l'Université de Montréal-Hôtel-Dieu, ²Département de Médecine and ³Groupe d’Étude des Protéines Membranaires, Département de Physiologie, Université de Montréal, Montréal, Québec, Canada

Submitted 14 September 2006 ; accepted in final form 12 July 2007

Several respiratory diseases are associated with extensive damage of lung epithelia, and the regulatory mechanisms involved in their regeneration are not clearly defined. Growth factors released by epithelial cells or fibroblasts from injured lungs are important regulators of alveolar repair by stimulating cell motility, proliferation, and differentiation. In addition, K⁺ channels regulate cell proliferation/migration and are coupled with growth factor signaling in several tissues. We decided to explore the hypothesis, never investigated before, that K⁺ could play a prominent role in alveolar repair. We employed a model of mechanical wounding of rat alveolar type II epithelia, in primary culture, to study their response to injury. Wound healing was suppressed by one-half upon epidermal growth factor (EGF) titration with EGF-antibody (Ab) or erbB1/erbB2 tyrosine-kinase inhibition with AG-1478/AG-825. The addition of exogenous EGF slightly stimulated the alveolar wound healing and enhanced, by up to five times, alveolar cell migration measured in a Boyden-type chamber. Conditioned medium collected from injured alveolar monolayers also stimulated cell migration; this effect was abolished in the presence of EGF-Ab. The impact of K⁺ channel modulators was examined in basal and EGF-stimulated conditions. Wound healing was stimulated by pinacidil, an ATP-dependent K⁺ channel (K_ATP) activator, which also increased cell migration, by twofold, in basal conditions and potentiated the stimulatory effect of EGF. K_ATP or KvLQT1 inhibitors (glibenclamide, clofilium) reduced EGF-stimulated wound healing, cell migration, and proliferation. Finally, EGF stimulated K_ATP and KvLQT1 currents and channel expression. In summary, stimulation of K⁺ channels through autocrine activation of EGF receptors could play a crucial role in lung epithelia repair processes.

lung; adenosine 5'-triphosphate-stimulated potassium channel; KvLQT1 K⁺ channels; epidermal growth factor; alveolar cell repair; migration; proliferation