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Long-term exposure to muscarinic agonists decreases expression of contractile proteins and responsiveness of rabbit tracheal smooth muscle cells
dc.creator | Stamatiou, R. | en |
dc.creator | Paraskeva, E. | en |
dc.creator | Vasilaki, A. | en |
dc.creator | Mylonis, I. | en |
dc.creator | Molyvdas, P. A. | en |
dc.creator | Gourgoulianis, K. | en |
dc.creator | Hatziefthimiou, A. | en |
dc.date.accessioned | 2015-11-23T10:48:30Z | |
dc.date.available | 2015-11-23T10:48:30Z | |
dc.date.issued | 2014 | |
dc.identifier | 10.1186/1471-2466-14-39 | |
dc.identifier.issn | 1471-2466 | |
dc.identifier.uri | http://hdl.handle.net/11615/33344 | |
dc.description.abstract | Background: Chronic airway diseases, like asthma or COPD, are characterized by excessive acetylcholine release and airway remodeling. The aim of this study was to investigate the long-term effect of muscarinic agonists on the phenotype and proliferation of rabbit tracheal airway smooth muscle cells (ASMCs). Methods: ASMCs were serum starved before treatment with muscarinic agonists. Cell phenotype was studied by optical microscopy and indirect immunofluorescence, using smooth muscle a-actin, desmin and SM-Myosin Heavy Chain (SM-MHC) antibodies. [N-methyl-H-3] scopolamine binding studies were performed in order to assess M-3 muscarinic receptor expression on isolated cell membranes. Contractility studies were performed on isolated ASMCs treated with muscarinic agonists. Proliferation was estimated using methyl-[3H] thymidine incorporation, MTT or cell counting methods. Involvement of PI3K and MAPK signalling pathways was studied by cell incubation with the pathway inhibitors LY294002 and PD98059 respectively. Results: Prolonged culture of ASMCs with acetylcholine, carbachol or FBS, reduced the expression of a-actin, desmin and SM-MHC compared to cells cultured in serum free medium. Treatment of ASMCs with muscarinic agonists for 3-15 days decreased muscarinic receptor expression and their responsiveness to muscarinic stimulation. Acetylcholine and carbachol induced DNA synthesis and increased cell number, of ASMCs that had acquired a contractile phenotype by 7 day serum starvation. This effect was mediated via a PI3K and MAPK dependent mechanism. Conclusions: Prolonged exposure of rabbit ASMCs to muscarinic agonists decreases the expression of smooth muscle specific marker proteins, down-regulates muscarinic receptors and decreases ASMC contractile responsiveness. Muscarinic agonists are mitogenic, via the PI3K and MAPK signalling pathways. | en |
dc.source.uri | <Go to ISI>://WOS:000335356400001 | |
dc.subject | Airway smooth muscle | en |
dc.subject | Acetylcholine | en |
dc.subject | Carbachol | en |
dc.subject | Phenotype | en |
dc.subject | Proliferation | en |
dc.subject | ACETYLCHOLINE-RECEPTORS | en |
dc.subject | UNCONTROLLED ASTHMA | en |
dc.subject | TIOTROPIUM BROMIDE | en |
dc.subject | PROLIFERATION | en |
dc.subject | ACTIVATION | en |
dc.subject | MECHANISMS | en |
dc.subject | PHENOTYPE | en |
dc.subject | PLASTICITY | en |
dc.subject | KINASE | en |
dc.subject | Respiratory System | en |
dc.title | Long-term exposure to muscarinic agonists decreases expression of contractile proteins and responsiveness of rabbit tracheal smooth muscle cells | en |
dc.type | journalArticle | en |
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