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

Reproductive Biology and Endocrinology

Rachel M. Tribe³  Michael J. Taggart¹  Donna M. Slater²  Frances R. Willey³  Evonne C. Chin-Smith³ 

[1] Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne NE2 4HH, UK;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;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

关键词: Transcription factors;    Stretch;    NFAT;    Uterine smooth muscle;    A23187;   

Others  :  1225468
DOI  :  10.1186/s12958-015-0086-0

 received in 2015-01-07, accepted in 2015-07-30,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Chin-Smith et al.

【 图 表 】

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