Laminin-binding integrin alpha7 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 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.
Tran
Thai
T
Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Ens-Blackie
Karen
K
Rector
Edward S
ES
Stelmack
Gerald L
GL
McNeill
Karol D
KD
Tarone
Guido
G
Gerthoffer
William T
WT
Unruh
Helmut
H
Halayko
Andrew J
AJ
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism*; D039422:Integrin alpha3 / Q000378:metabolism; D039503:Integrin alpha6 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism*; D009119:Muscle Contraction; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012137:Respiratory System / Q000166:cytology* / Q000378:metabolism*
D015703:Antigens, CD; D015415:Biomarkers; D039001:Integrin alpha Chains; D039422:Integrin alpha3; D039503:Integrin alpha6; D007797:Laminin; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C085725:integrin alpha7