Differential expression of peroxisome proliferator activated receptor γ and cyclin D1 does not affect proliferation of asthma-and non-asthma-derived airway smooth muscle cells

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Journal Article
Respirology, 2010, 15 (2), pp. 303 - 312
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Background and objective: Airway remodelling involves thickening of the airway smooth muscle (ASM) bulk. Proliferation of asthma-derived ASM cells is increased in vitro, but underlying mechanisms remain unknown. Peroxisome proliferators activated receptor-γ (PPARγ) regulates the cell cycle. It is suggested that PPARγ agonists have anti-inflammatory effects, which may be valuable in the treatment of asthma, but information regarding their antiproliferative properties in ASM is lacking. Although corticosteroids reduce airway inflammation, in vitro they inhibit proliferation in only non-asthma ASM cells by reducing cyclin D1. We therefore investigated the effects of mitogenic stimulation (foetal bovine serum (FBS)), and a PPARγ ligand (ciglitazone), on PPARγ and cyclin D1 expression and proliferation of ASM cells. In addition, we examined the effects of ciglitazone on ASM cell proliferation. Methods: We assessed PPARγ and cyclin D1 mRNA and protein levels using quantitative PCR and immunoblotting. Cell proliferation was assessed using bromodeoxyuridine uptake. Results: In the presence of 5% FBS, PPARγ and cyclin D1 expression decreased over time in non-asthmatic cells but increased in asthmatic cells (compared with sub-confluent cells). FBS-induced proliferation of asthmatic cells increased at all time points, but occurred only at day 7 with non-asthmatic cells (compared with unstimulated time-matched control). Ciglitazone increased PPARγ expression in both groups, but did not alter cell proliferation, while fluticasone increased PPARγ protein only in asthmatic cells. Conclusions: Although in the presence of a mitogenic stimulus, PPARγ was differentially expressed in asthma-and non-asthma-derived ASM; its expression was not related to the increased proliferation observed in asthmatic ASM. © 2009 Asian Pacific Society of Respirology.
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