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Caveolin-1 is required for contractile phenotype expression by airway smooth muscle cells

Airway smooth muscle cells exhibit phenotype plasticity that underpins their ability to contribute both to acute bronchospasm and to the features of airway remodelling in chronic asthma. A feature of mature, contractile smooth muscle cells is the presence of abundant caveolae, plasma membrane invagi...

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Autores principales: Gosens, Reinoud, Stelmack, Gerald L, Bos, Sophie T, Dueck, Gordon, Mutawe, Mark M, Schaafsma, Dedmer, Unruh, Helmut, Gerthoffer, William T, Zaagsma, Johan, Meurs, Herman, Halayko, Andrew J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822954/
https://www.ncbi.nlm.nih.gov/pubmed/21199324
http://dx.doi.org/10.1111/j.1582-4934.2010.01246.x
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author Gosens, Reinoud
Stelmack, Gerald L
Bos, Sophie T
Dueck, Gordon
Mutawe, Mark M
Schaafsma, Dedmer
Unruh, Helmut
Gerthoffer, William T
Zaagsma, Johan
Meurs, Herman
Halayko, Andrew J
author_facet Gosens, Reinoud
Stelmack, Gerald L
Bos, Sophie T
Dueck, Gordon
Mutawe, Mark M
Schaafsma, Dedmer
Unruh, Helmut
Gerthoffer, William T
Zaagsma, Johan
Meurs, Herman
Halayko, Andrew J
author_sort Gosens, Reinoud
collection PubMed
description Airway smooth muscle cells exhibit phenotype plasticity that underpins their ability to contribute both to acute bronchospasm and to the features of airway remodelling in chronic asthma. A feature of mature, contractile smooth muscle cells is the presence of abundant caveolae, plasma membrane invaginations that develop from the association of lipid rafts with caveolin-1, but the functional role of caveolae and caveolin-1 in smooth muscle phenotype plasticity is unknown. Here, we report a key role for caveolin-1 in promoting phenotype maturation of differentiated airway smooth muscle induced by transforming growth factor (TGF)-β(1). As assessed by Western analysis and laser scanning cytometry, caveolin-1 protein expression was selectively enriched in contractile phenotype airway myocytes. Treatment with TGF-β(1) induced profound increases in the contractile phenotype markers sm-α-actin and calponin in cells that also accumulated abundant caveolin-1; however, siRNA or shRNAi inhibition of caveolin-1 expression largely prevented the induction of these contractile phenotype marker proteins by TGF-β(1). The failure by TGF-β(1) to adequately induce the expression of these smooth muscle specific proteins was accompanied by a strongly impaired induction of eukaryotic initiation factor-4E binding protein(4E-BP)1 phosphorylation with caveolin-1 knockdown, indicating that caveolin-1 expression promotes TGF-β(1) signalling associated with myocyte maturation and hypertrophy. Furthermore, we observed increased expression of caveolin-1 within the airway smooth muscle bundle of guinea pigs repeatedly challenged with allergen, which was associated with increased contractile protein expression, thus providing in vivo evidence linking caveolin-1 expression with accumulation of contractile phenotype myocytes. Collectively, we identify a new function for caveolin-1 in controlling smooth muscle phenotype; this mechanism could contribute to allergic asthma.
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spelling pubmed-38229542015-01-26 Caveolin-1 is required for contractile phenotype expression by airway smooth muscle cells Gosens, Reinoud Stelmack, Gerald L Bos, Sophie T Dueck, Gordon Mutawe, Mark M Schaafsma, Dedmer Unruh, Helmut Gerthoffer, William T Zaagsma, Johan Meurs, Herman Halayko, Andrew J J Cell Mol Med Original Articles Airway smooth muscle cells exhibit phenotype plasticity that underpins their ability to contribute both to acute bronchospasm and to the features of airway remodelling in chronic asthma. A feature of mature, contractile smooth muscle cells is the presence of abundant caveolae, plasma membrane invaginations that develop from the association of lipid rafts with caveolin-1, but the functional role of caveolae and caveolin-1 in smooth muscle phenotype plasticity is unknown. Here, we report a key role for caveolin-1 in promoting phenotype maturation of differentiated airway smooth muscle induced by transforming growth factor (TGF)-β(1). As assessed by Western analysis and laser scanning cytometry, caveolin-1 protein expression was selectively enriched in contractile phenotype airway myocytes. Treatment with TGF-β(1) induced profound increases in the contractile phenotype markers sm-α-actin and calponin in cells that also accumulated abundant caveolin-1; however, siRNA or shRNAi inhibition of caveolin-1 expression largely prevented the induction of these contractile phenotype marker proteins by TGF-β(1). The failure by TGF-β(1) to adequately induce the expression of these smooth muscle specific proteins was accompanied by a strongly impaired induction of eukaryotic initiation factor-4E binding protein(4E-BP)1 phosphorylation with caveolin-1 knockdown, indicating that caveolin-1 expression promotes TGF-β(1) signalling associated with myocyte maturation and hypertrophy. Furthermore, we observed increased expression of caveolin-1 within the airway smooth muscle bundle of guinea pigs repeatedly challenged with allergen, which was associated with increased contractile protein expression, thus providing in vivo evidence linking caveolin-1 expression with accumulation of contractile phenotype myocytes. Collectively, we identify a new function for caveolin-1 in controlling smooth muscle phenotype; this mechanism could contribute to allergic asthma. Blackwell Publishing Ltd 2011-11 2011-10-24 /pmc/articles/PMC3822954/ /pubmed/21199324 http://dx.doi.org/10.1111/j.1582-4934.2010.01246.x Text en © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Original Articles
Gosens, Reinoud
Stelmack, Gerald L
Bos, Sophie T
Dueck, Gordon
Mutawe, Mark M
Schaafsma, Dedmer
Unruh, Helmut
Gerthoffer, William T
Zaagsma, Johan
Meurs, Herman
Halayko, Andrew J
Caveolin-1 is required for contractile phenotype expression by airway smooth muscle cells
title Caveolin-1 is required for contractile phenotype expression by airway smooth muscle cells
title_full Caveolin-1 is required for contractile phenotype expression by airway smooth muscle cells
title_fullStr Caveolin-1 is required for contractile phenotype expression by airway smooth muscle cells
title_full_unstemmed Caveolin-1 is required for contractile phenotype expression by airway smooth muscle cells
title_short Caveolin-1 is required for contractile phenotype expression by airway smooth muscle cells
title_sort caveolin-1 is required for contractile phenotype expression by airway smooth muscle cells
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822954/
https://www.ncbi.nlm.nih.gov/pubmed/21199324
http://dx.doi.org/10.1111/j.1582-4934.2010.01246.x
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