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Nuclear factor of activated T-cell isoform expression and regulation in human myometrium

Lookup NU author(s): Professor Michael TaggartORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 Ca2+ 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 mu M) 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 mu M).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.


Publication metadata

Author(s): Chin-Smith EC, Willey FR, Slater DM, Taggart MJ, Tribe RM

Publication type: Article

Publication status: Published

Journal: Reproductive Biology and Endocrinology

Year: 2015

Volume: 13

Online publication date: 04/08/2015

Acceptance date: 30/07/2015

Date deposited: 05/04/2016

ISSN (electronic): 1477-7827

Publisher: BioMed Central Ltd

URL: http://dx.doi.org/10.1186/s12958-015-0086-0

DOI: 10.1186/s12958-015-0086-0


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Funding

Funder referenceFunder name
King's College London School of Medicine PhD studentship
1060508Tommy's Charity

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