Submitted on May 9, 2007
Revised on July 19, 2007
Laminin-binding Integrin 
7 is Required for Contractile Phenotype Expression by Human Airway Myocyte
Thai Tran1*, Karen Ens-Blackie1, Edward S Rector2, Gerald L Stelmack1, Karol D McNeill1, Guido Tarone3, William T Gerthoffer4, Helmut Unruh5, and Andrew J Halayko1
1 Department of Physiology and Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Manitoba Institute of Child Health, Biology of Breathing Group, Winnipeg, Manitoba, Canada; Universtiy of Manitoba, CIHR National Training Program in Allergy and Asthma, Winnipeg, Manitoba, Canada,
2 University of Manitoba, Flow Cytometry Laboratory, Winnipeg, Manitoba, Canada,
3 Dipartimento di Genetica, Biologia e Biochimica, Universita di Torino, Molecular Biotechnology Center, Torino, Italy,
4 Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada, USA,
5 University of Manitoba, Sections of Respiratory Diseases and Thoracic Surgery, Winnipeg, Manitoba, Canada
* To whom correspondence should be addressed. E-mail: ttran{at}mich.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 modelling and remodelling 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, 
3
1, 61, and 71, 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 3A, 6A and 7B. Flow cytometry revealed that 7B expression was a distinct feature of individual myocytes that acquired a contractile phenotype. siRNA knockdown of 7, but not 3 or 6, suppressed myocyte maturation. Thus, 7B is a novel marker of the contractile phenotype, and 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 remodelling associated with airways disease.
