Laminin-Binding Integrin α7 Is Required for Contractile Phenotype Expression by Human Airway Myocytes

Autor: Helmut Unruh, Karol D. McNeill, Andrew J. Halayko, Karen Ens-Blackie, Edward S. Rector, Gerald L. Stelmack, William T. Gerthoffer, Guido Tarone, Thai Tran
Rok vydání: 2007
Předmět:
Zdroj: American Journal of Respiratory Cell and Molecular Biology. 37:668-680
ISSN: 1535-4989
1044-1549
Popis: Contractile airway smooth muscle (ASM) cells retain the ability for phenotype plasticity in response to multiple stimuli, which equips them with capacity to direct modeling and remodeling during development, and in disease states such as asthma. We have shown that endogenously expressed laminin is required for maturation of human ASM cells to a contractile phenotype, as occurs during ASM thickening in asthma. In this study, we profiled the expression of laminin-binding integrins alpha3beta1, alpha6beta1, and alpha7beta1, and tested whether they are required for laminin-induced myocyte maturation. Immunoblotting revealed that myocyte maturation induced by prolonged serum withdrawal, which was marked by the accumulation of contractile phenotype marker protein desmin, was also associated with the accumulation of alpha3A, alpha6A, and alpha7B. Flow cytometry revealed that alpha7B expression was a distinct feature of individual myocytes that acquired a contractile phenotype. siRNA knockdown of alpha7, but not alpha3 or alpha6, suppressed myocyte maturation. Thus, alpha7B is a novel marker of the contractile phenotype, and alpha7 expression is essential for human ASM cell maturation, which is a laminin-dependent process. These observations provide new insight into mechanisms that likely underpin normal development and remodeling associated with airways disease.
Databáze: OpenAIRE