title: Characterization of the dystrophin-glycoprotein complex in airway smooth muscle: role of δ-sarcoglycan in airway responsiveness.
abstract: The dystrophin-glycoprotein complex (DGC) is an integral part of caveolae microdomains, and its interaction with caveolin-1 is essential for the phenotype and functional properties of airway smooth muscle (ASM). The sarcoglycan complex provides stability to the dystroglycan complex, but its role in ASM contraction and lung physiology in not understood. We tested whether δ-sarcoglycan (δ-SG), through its interaction with the DGC, is a determinant of ASM contraction ex vivo and airway mechanics in vivo. We measured methacholine (MCh)-induced isometric contraction and airway mechanics in δ-SG KO and wild-type mice. Last, we performed immunoblotting and transmission electron microscopy to assess DGC protein expression and the ultrastructural features of tracheal smooth muscle. Our results reveal an age-dependent reduction in the MCh-induced tracheal isometric force and significant reduction in airway resistance at high concentrations of MCh (50.0 mg/mL) in δ-SG KO mice. The changes in contraction and lung function correlated with decreased caveolin-1 and β-dystroglycan abundance, as well as an age-dependent loss of caveolae in the cell membrane of tracheal smooth muscle in δ-SG KO mice. Collectively, these results confirm and extend understanding of a functional role for the DGC in the contractile properties of ASM and demonstrate that this results in altered lung function in vivo.
authors.affiliation: Departments of Physiology and Pathophysiology, University of Manitoba, John Buhler Research Centre, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada., Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada.
authors.forename: Pawan
authors.initials: P
authors.lastname: Sharma
authors.forename: Aruni
authors.initials: A
authors.lastname: Jha
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Stelmack
authors.forename: Karen
authors.initials: K
authors.lastname: Detillieux
authors.forename: Sujata
authors.initials: S
authors.lastname: Basu
authors.forename: Thomas
authors.initials: T
authors.lastname: Klonisch
authors.forename: Helmut
authors.initials: H
authors.lastname: Unruh
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Halayko
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D051242:Caveolin 1 / Q000378:metabolism; D004285:Dogs; D049030:Dystroglycans / Q000378:metabolism; D016189:Dystrophin / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D008168:Lung / Q000187:drug effects*; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000187:drug effects*; D049031:Sarcoglycans / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects
chemical_list: D016085:Bronchoconstrictor Agents; D051242:Caveolin 1; D016189:Dystrophin; D006023:Glycoproteins; D049031:Sarcoglycans; D016210:Methacholine Chloride; D049030:Dystroglycans
keywords: airway responsiveness; airway smooth muscle; caveolae; cavéole; complexe dystrophine glycoprotéine; contraction; dystrophin glycoprotein complex; muscle lisse respiratoire; réactivité bronchique