Laminin-binding integrin α7 is required for contractile phenotype expression by human airway myocytes

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 alpha 3 beta 1, alpha 6 beta 1, and alpha 7 beta 1, 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 alpha 3A, alpha 6A, and alpha 7B. Flow cytometry revealed that alpha 7 beta expression was a distinct feature of individual myocytes that acquired a contractile phenotype. siRNA knockdown of alpha 7, but not alpha 3 or alpha 6, suppressed myocyte maturation. Thus, alpha 7B is a novel marker of the contractile phenotype, and alpha 7 expression is essential for human ASM cell maturation, which is a laminin-dependent process. These observations provide new in- sight into mechanisms that likely underpin normal development and remodeling associated with airways disease.