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Published ahead of print on July 19, 2007, doi:10.1165/rcmb.2007-0165OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 37, pp. 668-680, 2007
© 2007 American Thoracic Society
DOI: 10.1165/rcmb.2007-0165OC

Laminin-Binding Integrin {alpha}7 Is Required for Contractile Phenotype Expression by Human Airway Myocytes

Thai Tran1,2,5, Karen Ens-Blackie1,2,5, Edward S. Rector3, Gerald L. Stelmack1,2,5, Karol D. McNeill1,2,5, Guido Tarone6, William T. Gerthoffer7, Helmut Unruh4 and Andrew J. Halayko1,2,4,5

1 Departments of Physiology and Internal Medicine, 2 CIHR National Training Program in Allergy and Asthma, 3 Flow Cytometry Laboratory, and 4 Sections of Respiratory Diseases and Thoracic Surgery, University of Manitoba, Winnipeg, Manitoba, Canada; 5 Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada; 6 Dipartimento di Genetica, Biologia e Biochimica, Molecular Biotechnology Center, Università di Torino, Torino, Italy; and 7 Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada

Correspondence and requests for reprints should be addressed to Andrew J. Halayko, Section of Respiratory Disease, University of Manitoba, Room RS321, 810 Sherbrook Street, Winnipeg, MB, R3A 1R8 Canada. E-mail: ahalayk{at}cc.umanitoba.ca

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}3beta1, {alpha}6beta1, and {alpha}7beta1, 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}7B 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 insight into mechanisms that likely underpin normal development and remodeling associated with airways disease.

Key Words: airway remodeling • asthma • desmin • extracellular matrix • phenotype plasticity


CLINICAL RELEVANCE

This study reveals new biological mechanisms relevant to fibroproliferative disorders such as asthma that are characterized by the accumulation of smooth muscle, and in which smooth muscle phenotype switching occurs.

 



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