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dc.creatorStamatiou, R.en
dc.creatorParaskeva, E.en
dc.creatorVasilaki, A.en
dc.creatorMylonis, I.en
dc.creatorMolyvdas, P. A.en
dc.creatorGourgoulianis, K.en
dc.creatorHatziefthimiou, A.en
dc.date.accessioned2015-11-23T10:48:30Z
dc.date.available2015-11-23T10:48:30Z
dc.date.issued2014
dc.identifier10.1186/1471-2466-14-39
dc.identifier.issn1471-2466
dc.identifier.urihttp://hdl.handle.net/11615/33344
dc.description.abstractBackground: 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.subjectAirway smooth muscleen
dc.subjectAcetylcholineen
dc.subjectCarbacholen
dc.subjectPhenotypeen
dc.subjectProliferationen
dc.subjectACETYLCHOLINE-RECEPTORSen
dc.subjectUNCONTROLLED ASTHMAen
dc.subjectTIOTROPIUM BROMIDEen
dc.subjectPROLIFERATIONen
dc.subjectACTIVATIONen
dc.subjectMECHANISMSen
dc.subjectPHENOTYPEen
dc.subjectPLASTICITYen
dc.subjectKINASEen
dc.subjectRespiratory Systemen
dc.titleLong-term exposure to muscarinic agonists decreases expression of contractile proteins and responsiveness of rabbit tracheal smooth muscle cellsen
dc.typejournalArticleen


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