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

Gosens R, Stelmack GL, Bos ST, Dueck G, Mutawe MM, Schaafsma D, Unruh H, Gerthoffer WT, Zaagsma J, Meurs H, Halayko AJ - J. Cell. Mol. Med. (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.

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Increased caveolin-1 expression in the airway smooth muscle bundle of allergen challenged guinea pigs. Ovalbumin sensitized guinea pigs were challenged using ovalbumin once a week for 12 weeks. Twenty-four hours after the last allergen exposure, lung tissue was collected for further analyses. (A) Airway smooth muscle expression of caveolin-1 was determined using immunohistochemical analysis for caveolin-1 which showed a clear positive staining within the airway smooth muscle bundle. Airway smooth muscle bundles in sections of saline challenged animals or ovalbumin challenged animals were then digitally photographed and caveolin-1 intensity was quantified. Densitometric data shown in (B) are the means ± S.E. of five saline and five ovalbumin challenged animals. Inflammatory cells within the muscle bundle were excluded from the quantification procedure. Differences between data were analysed by a two-tailed Student’s t-test for unpaired observations; *P < 0.05.
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fig06: Increased caveolin-1 expression in the airway smooth muscle bundle of allergen challenged guinea pigs. Ovalbumin sensitized guinea pigs were challenged using ovalbumin once a week for 12 weeks. Twenty-four hours after the last allergen exposure, lung tissue was collected for further analyses. (A) Airway smooth muscle expression of caveolin-1 was determined using immunohistochemical analysis for caveolin-1 which showed a clear positive staining within the airway smooth muscle bundle. Airway smooth muscle bundles in sections of saline challenged animals or ovalbumin challenged animals were then digitally photographed and caveolin-1 intensity was quantified. Densitometric data shown in (B) are the means ± S.E. of five saline and five ovalbumin challenged animals. Inflammatory cells within the muscle bundle were excluded from the quantification procedure. Differences between data were analysed by a two-tailed Student’s t-test for unpaired observations; *P < 0.05.

Mentions: Our current results and published data [6–8] indicate a role for caveolin-1 in contractile function and contractile phenotype maturation of airway smooth muscle. Increased contraction of smooth muscle, and increased expression of contractile phenotype markers are characteristic for asthma, and can be mimicked in animal models of asthma [43]. Guinea pigs repeatedly challenged with ovalbumin develop airway hyperresponsiveness, airway smooth muscle thickening, increased pulmonary contractile protein expression and increased contractile capacity of airway smooth muscle [41]. Thus, to determine whether our in vitro findings were related to increased contractile airway smooth muscle mass in vivo, we determined caveolin-1 expression by airway smooth muscle using guinea pigs subjected to repeated allergen exposure. As demonstrated in Figure 5A and B, Western analysis of whole lung indicated that repeated allergen exposures increased caveolin-1 expression. The increase in caveolin-1 was due, in part, to a specific increase in its expression by the airway smooth muscle, as determined using quantitative immunohistochemistry (Fig. 6A and B). These data mimic these we have reported for contractile phenotype marker proteins [42, 43]. Thus, it appears that increased caveolin-1 expression is a feature of allergen-induced airway smooth muscle remodelling in this animal model.


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

Gosens R, Stelmack GL, Bos ST, Dueck G, Mutawe MM, Schaafsma D, Unruh H, Gerthoffer WT, Zaagsma J, Meurs H, Halayko AJ - J. Cell. Mol. Med. (2011)

Increased caveolin-1 expression in the airway smooth muscle bundle of allergen challenged guinea pigs. Ovalbumin sensitized guinea pigs were challenged using ovalbumin once a week for 12 weeks. Twenty-four hours after the last allergen exposure, lung tissue was collected for further analyses. (A) Airway smooth muscle expression of caveolin-1 was determined using immunohistochemical analysis for caveolin-1 which showed a clear positive staining within the airway smooth muscle bundle. Airway smooth muscle bundles in sections of saline challenged animals or ovalbumin challenged animals were then digitally photographed and caveolin-1 intensity was quantified. Densitometric data shown in (B) are the means ± S.E. of five saline and five ovalbumin challenged animals. Inflammatory cells within the muscle bundle were excluded from the quantification procedure. Differences between data were analysed by a two-tailed Student’s t-test for unpaired observations; *P < 0.05.
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Related In: Results  -  Collection

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fig06: Increased caveolin-1 expression in the airway smooth muscle bundle of allergen challenged guinea pigs. Ovalbumin sensitized guinea pigs were challenged using ovalbumin once a week for 12 weeks. Twenty-four hours after the last allergen exposure, lung tissue was collected for further analyses. (A) Airway smooth muscle expression of caveolin-1 was determined using immunohistochemical analysis for caveolin-1 which showed a clear positive staining within the airway smooth muscle bundle. Airway smooth muscle bundles in sections of saline challenged animals or ovalbumin challenged animals were then digitally photographed and caveolin-1 intensity was quantified. Densitometric data shown in (B) are the means ± S.E. of five saline and five ovalbumin challenged animals. Inflammatory cells within the muscle bundle were excluded from the quantification procedure. Differences between data were analysed by a two-tailed Student’s t-test for unpaired observations; *P < 0.05.
Mentions: Our current results and published data [6–8] indicate a role for caveolin-1 in contractile function and contractile phenotype maturation of airway smooth muscle. Increased contraction of smooth muscle, and increased expression of contractile phenotype markers are characteristic for asthma, and can be mimicked in animal models of asthma [43]. Guinea pigs repeatedly challenged with ovalbumin develop airway hyperresponsiveness, airway smooth muscle thickening, increased pulmonary contractile protein expression and increased contractile capacity of airway smooth muscle [41]. Thus, to determine whether our in vitro findings were related to increased contractile airway smooth muscle mass in vivo, we determined caveolin-1 expression by airway smooth muscle using guinea pigs subjected to repeated allergen exposure. As demonstrated in Figure 5A and B, Western analysis of whole lung indicated that repeated allergen exposures increased caveolin-1 expression. The increase in caveolin-1 was due, in part, to a specific increase in its expression by the airway smooth muscle, as determined using quantitative immunohistochemistry (Fig. 6A and B). These data mimic these we have reported for contractile phenotype marker proteins [42, 43]. Thus, it appears that increased caveolin-1 expression is a feature of allergen-induced airway smooth muscle remodelling in this animal model.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.

Show MeSH
Related in: MedlinePlus