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dc.contributor.authorFitzgibbon, Joan
dc.contributor.authorMorrison, John J.
dc.contributor.authorSmith, Terry
dc.contributor.authorO'Brien, Margaret
dc.date.accessioned2014-01-23T13:52:01Z
dc.date.available2014-01-23T13:52:01Z
dc.date.issued2009-01-08
dc.identifier.citationFitzgibbon, J,Morrison, JJ,Smith, TJ,O'Brien, M (2009) 'Modulation of human uterine smooth muscle cell collagen contractility by thrombin, Y-27632, TNF alpha and indomethacin'. Reproductive Biology And Endocrinology, 7 .en_US
dc.identifier.urihttp://hdl.handle.net/10379/4015
dc.descriptionJournal article (open access)en_US
dc.description.abstractBackground: Preterm labour occurs in approximately 10% of pregnancies and is a major cause of infant morbidity and mortality. However, the pathways involved in regulating contractility in normal and preterm labour are not fully elucidated. Our aim was to utilise a human myometrial contractility model to investigate the effect of a number of uterine specific contractility agents in this system. Therefore, we investigated the contractile response of human primary uterine smooth muscle cells or immortalised myometrial smooth muscle cells cultured within collagen lattices, to known mediators of uterine contractility, which included thrombin, the ROCK-1 inhibitor Y-27632, tumour necrosis factor alpha (TNF alpha) and the non-steroidal anti-inflammatory indomethacin.Methods: Cell contractility was calculated over time, with the collagen gel contraction assay, utilising human primary uterine smooth muscle cells (hUtSMCs) and immortalised myometrial smooth muscle cells (hTERT-HM): a decrease in collagen gel area equated to an increase in contractility. RNA was isolated from collagen embedded cells and gene expression changes were analysed by real time fluorescence reverse transcription polymerase chain reaction. Scanning electron and fluorescence microscopy were employed to observe cell morphology and cell collagen gel interactions. Statistical analysis was performed using ANOVA followed by Tukey's post hoc tests.Results: TNF alpha increased collagen contractility in comparison to the un-stimulated collagen embedded hUtSMC cells, which was inhibited by indomethacin, while indomethacin alone significantly inhibited contraction. Thrombin augmented the contractility of uterine smooth muscle cell and hTERT-HM collagen gels, this effect was inhibited by the thrombin specific inhibitor, hirudin. Y-27632 decreased both basal and thrombin-induced collagen contractility in the hTERT-HM embedded gels. mRNA expression of the thrombin receptor, F2R was up-regulated in hUtSMCs isolated from collagen gel lattices, following thrombin-stimulated contractility.Conclusion: TNF alpha and thrombin increased uterine smooth muscle cell collagen contractility while indomethacin had the opposite effect. Thrombin-induced collagen contractility resulted in F2R activation which may in part be mediated by the ROCK-1 pathway. This study established the in vitro human myometrial model as a viable method to assess the effects of a range of uterotonic or uterorelaxant agents on contractility, and also permits investigation of the complex regulatory pathways involved in mediating myometrial contractility at labour.en_US
dc.description.sponsorshipHealth Research Board of Irelanden_US
dc.formatapplication/pdfen_US
dc.language.isoenen_US
dc.publisherBioMed Centralen_US
dc.relation.ispartofReproductive Biology And Endocrinologyen
dc.subjectTumor-necrosis-factoren_US
dc.subjectProtease-activated receptorsen_US
dc.subjectPreterm deliveryen_US
dc.subjectIn-vitroen_US
dc.subjectMyometriumen_US
dc.subjectLabouren_US
dc.subjectParturitionen_US
dc.subjectKinaseen_US
dc.subjectTermen_US
dc.subjectFibroblastsen_US
dc.titleModulation of human uterine smooth muscle cell collagen contractility by thrombin, Y-27632, TNF alpha and indomethacinen_US
dc.typeArticleen_US
dc.date.updated2013-10-07T15:28:38Z
dc.identifier.doi10.1186/1477-7827-7-2
dc.local.publishedsourcehttp://dx.doi.org/10.1186/1477-7827-7-2en_US
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funder|~|
dc.internal.rssid1053812
dc.local.contactTerry Smith, School Of Natural Sciences, Nui Galway. 5488 Email: terry.smith@nuigalway.ie
dc.local.copyrightcheckedNo
dc.local.versionACCEPTED
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