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dc.contributor.author Tran, Thai
dc.contributor.author McNeill, Karol D
dc.contributor.author Gerthoffer, William T
dc.contributor.author Unruh, Helmut
dc.contributor.author Halayko, Andrew J
dc.date.accessioned 2016-01-25T21:31:43Z
dc.date.available 2016-01-25T21:31:43Z
dc.date.issued 2006-09-12
dc.identifier.citation Respiratory Research. 2006 Sep 12;7(1):117
dc.identifier.uri http://dx.doi.org/10.1186/1465-9921-7-117
dc.identifier.uri http://hdl.handle.net/1993/31115
dc.description.abstract Abstract Background Airway smooth muscle (ASM) contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM) components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. Methods Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. Results Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP) significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. Conclusion While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the first time that endogenously expressed laminin is required for ASM maturation to the contractile phenotype. As endogenously expressed laminin chains α2, β1 and γ1 are uniquely increased during myocyte maturation, these laminin chains may be key in this process. Thus, human ASM maturation appears to involve regulated endogenous expression of a select set of laminin chains that are essential for accumulation of contractile phenotype myocytes.
dc.rights info:eu-repo/semantics/openAccess
dc.title Endogenous laminin is required for human airway smooth muscle cell maturation
dc.type Journal Article
dc.type info:eu-repo/semantics/article
dc.language.rfc3066 en
dc.rights.holder Tran et al.
dc.date.updated 2016-01-25T17:02:58Z


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