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dc.contributor.supervisor Halayko, Andrew (Physiology) en_US
dc.contributor.author Maltby, Sarah
dc.date.accessioned 2011-09-08T13:43:44Z
dc.date.available 2011-09-08T13:43:44Z
dc.date.issued 2011-09-08
dc.identifier.uri http://hdl.handle.net/1993/4849
dc.description.abstract Caveolin-1 is a marker protein for caveolae and can be a regulator of intracellular signaling pathways that contribute to the pathogenesis of human diseases. In the present study, the structural and functional changes of the lung in caveolin-1 null mice (Cav-1-/-) were assessed. Respiratory mechanics, measured using a small animal ventilator, revealed heightened central airway resistance (Rn), tissue resistance (G) and tissue elastance (H) in response to inhaled methacholine. The respiratory hyperreactivity is associated with increased collagen deposition around central and peripheral airways in Cav-1-/- mice; however, no difference was found in smooth muscle α-actin quantity between mouse strains. Similar to our in vivo findings, tracheal rings from Cav-1-/- mice mounted on an isometric wire myograph exhibited enhanced maximum active contractile force without a change in sensitivity (EC50) to methacholine. Rho kinase (ROCK1/2), protein kinase C (PKC) and extracellular signal regulated kinase 1/2 (ERK1/2) signaling were assessed as possible sources of the enhanced airway reactivity observed in Cav-1-/- mice. Inhibition of Rho kinase markedly blunted in vivo lung function responses (Rn) and (G) and ex vivo smooth muscle responses to methacholine. In fact, inhibition of Rho kinase completely eliminated any difference in response between mouse strains. Thus, our data indicate that Cav-1 may regulate mechanisms, such as Rho/Rho kinase signaling, that determine airway smooth muscle contraction and airway fibrosis; thus, it could be an important regulator of airway biology and physiology in health and disease. en_US
dc.subject Caveolin-1 en_US
dc.subject airway smooth muscle en_US
dc.title Characterization of caveolin-1 as a modulator of airway smooth muscle responsiveness ex vivo and in vivo en_US
dc.degree.discipline Physiology en_US
dc.contributor.examiningcommittee Fedirchuk, Brent (Physiology) Soussi-Gounni, Abdelilah (Immunology) Kroeger, Edwin (Physiology) en_US
dc.degree.level Master of Science (M.Sc.) en_US
dc.description.note October 2011 en_US


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