• Open Access

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

Authors

  • Reinoud Gosens,

    1. Departments of Physiology & Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    2. Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada
    3. Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands
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  • Gerald L. Stelmack,

    1. Departments of Physiology & Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    2. Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada
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  • Sophie T. Bos,

    1. Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands
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  • Gordon Dueck,

    1. Departments of Physiology & Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    2. Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada
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  • Mark M. Mutawe,

    1. Departments of Physiology & Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    2. Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada
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  • Dedmer Schaafsma,

    1. Departments of Physiology & Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    2. Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada
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  • Helmut Unruh,

    1. Section of Thoracic Surgery, University of Manitoba, Winnipeg, Manitoba, Canada
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  • William T. Gerthoffer,

    1. Department of Pharmacology, University of Nevada School of Medicine, Reno, NV, USA
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  • Johan Zaagsma,

    1. Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands
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  • Herman Meurs,

    1. Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands
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  • Andrew J. Halayko

    Corresponding author
    1. Departments of Physiology & Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    2. Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada
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Andrew J. HALAYKO, Department of Physiology, Section of Respiratory Disease, University of Manitoba, Respiratory Hospital, Rm. RS321–810, Sherbrook St., Winnipeg, MB R3A 1R8, Canada. Tel.: (204) 787 2062 Fax: (204) 787 1220 E-mail: ahalayk@cc.umanitoba.ca

Abstract

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)-β1. As assessed by Western analysis and laser scanning cytometry, caveolin-1 protein expression was selectively enriched in contractile phenotype airway myocytes. Treatment with TGF-β1 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-β1. The failure by TGF-β1 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-β1 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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