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

Autor: Helmut Unruh, Andrew J. Halayko, Sophie Bos, Reinoud Gosens, Mark M. Mutawe, Gordon Dueck, Dedmer Schaafsma, Gerald L. Stelmack, William T. Gerthoffer, Johan Zaagsma, Herman Meurs
Přispěvatelé: Molecular Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC)
Jazyk: angličtina
Rok vydání: 2011
Předmět:
TGF-ss 1
Caveolin 1
Respiratory System
Muscle hypertrophy
DISRUPTS CAVEOLAE
CA2+
0302 clinical medicine
Caveolae
TGF-β1
Myocyte
RNA
Small Interfering
PHOSPHORYLATION
Cells
Cultured
DYSTROPHIN-GLYCOPROTEIN COMPLEX
0303 health sciences
biology
Microfilament Proteins
Phenotype
MAP KINASE ACTIVATION
Cell biology
FAMILY-MEMBERS
Molecular Medicine
Airway Remodeling
RNA Interference
medicine.symptom
MEMBRANE CHOLESTEROL
Muscle contraction
Muscle Contraction
Signal Transduction
Calponin
Guinea Pigs
Myocytes
Smooth Muscle
airway remodelling
Transforming Growth Factor beta1
03 medical and health sciences
Dogs
medicine
Animals
Humans
phenotype plasticity
Actin
030304 developmental biology
Muscle Cells
RECEPTOR
GROWTH-FACTOR-BETA
Calcium-Binding Proteins
Cell Biology
Original Articles
asthma
Actins
Eukaryotic Initiation Factor-4E
030228 respiratory system
caveolae
biology.protein
SEVERE ASTHMA
Zdroj: Journal of cellular and molecular medicine, 15(11), 2430-2442. Wiley
Journal of Cellular and Molecular Medicine
ISSN: 1582-1838
Popis: 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)-beta 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-beta 1 induced profound increases in the contractile phenotype markers sm-a-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-beta 1. The failure by TGF-beta 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-beta 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.
Databáze: OpenAIRE
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