title: Nuclear factor of activated T-cell isoform expression and regulation in human myometrium.
abstract: BACKGROUND
  During pregnancy, myometrial gene and protein expression is tightly regulated to accommodate fetal growth, promote quiescence and ultimately prepare for the onset of labour. It is proposed that changes in calcium signalling, may contribute to regulating gene expression and that nuclear factor of activated T-cell (NFAT) transcription factors (isoforms c1-c4) may be involved. Currently, there is little information regarding NFAT expression and regulation in myometrium.
  
  
  METHODS
  This study examined NFAT isoform mRNA expression in human myometrial tissue and cells from pregnant women using quantitative PCR. The effects of the Ca(2+) ionophore A23187 and in vitro stretch (25 % elongation, static strain; Flexercell FX-4000 Tension System) on NFAT expression were determined in cultured human myometrial cells.
  
  
  RESULTS
  Human myometrial tissue and cultured cells expressed NFATc1-c4 mRNA. NFATc2 gene expression in cultured cells was increased in response to 6 h stretch (11.5 fold, P < 0.001, n = 6) and calcium ionophore (A23187, 5 μM) treatment (20.6 fold, P < 0.001, n = 6). This response to stretch was significantly reduced (90 %, P < 0.001, n = 10) in the presence of an intracellular calcium chelator, BAPTA-AM (20 μM).
  
  
  CONCLUSIONS
  These data suggest that NFATc2 expression is regulated by intracellular calcium and in vitro stretch, and that the stretch response in human myometrial cells is dependent upon intracellular calcium signalling pathways. Our findings indicate a potentially unique role for NFATc2 in mediating stretch-induced gene expression per se and warrant further exploration in relation to the mechanisms promoting uterine smooth muscle growth in early pregnancy and/or labour.
authors.affiliation: Division of Women's Health, King's College London, Women's Health Academic Centre KHP, St Thomas' Hospital, 10th Floor, North Wing, Westminster Bridge Road, London, SE1 7EH, UK. evonne.chin-smith@kcl.ac.uk.
authors.forename: Evonne C
authors.initials: EC
authors.lastname: Chin-Smith
authors.affiliation: Division of Women's Health, King's College London, Women's Health Academic Centre KHP, St Thomas' Hospital, 10th Floor, North Wing, Westminster Bridge Road, London, SE1 7EH, UK. frances.willey@kpmg.co.uk.
authors.forename: Frances R
authors.initials: FR
authors.lastname: Willey
authors.affiliation: Physiology and Pharmacology, Cumming School of Medicine, Alberta Children's Hospital Research Institute for Child and Maternal Health, University of Calgary, Alberta, T2N 4 N1, Canada. dmslater@ucalgary.ca.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Slater
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, NE2 4HH, UK. michael.taggart@ncl.ac.uk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Taggart
authors.affiliation: Division of Women's Health, King's College London, Women's Health Academic Centre KHP, St Thomas' Hospital, 10th Floor, North Wing, Westminster Bridge Road, London, SE1 7EH, UK. rachel.tribe@kcl.ac.uk.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Tribe
mesh_terms: D000001:Calcimycin / Q000494:pharmacology; D061207:Calcium Ionophores / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014590:Uterine Contraction / Q000502:physiology
chemical_list: D061207:Calcium Ionophores; D050778:NFATC Transcription Factors; D020033:Protein Isoforms; D000001:Calcimycin