Nuclear factor of activated T-cell isoform expression and regulation in human myometrium.
Nuclear factor of activated T-cell isoform expression and regulation in human myometrium.
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DOI：
10.1186/s12958-015-0086-0
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发表时间：
2015-08-04
期刊：
影响因子：
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通讯作者：
Tribe RM
中科院分区：
文献类型：
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作者：
Chin-Smith EC;Willey FR;Slater DM;Taggart MJ;Tribe RM
在怀孕期间，子宫肌层基因和蛋白质表达受到严格调控，以适应胎儿生长，促进静止，并最终为分娩的开始做好准备。有人提出，钙信号的变化，可能有助于调节基因的表达和核因子活化T细胞（NFAT）转录因子（亚型C1-C4）可能参与。目前，关于NFAT在子宫肌层中的表达和调节的信息很少。本研究采用定量PCR技术检测了NFAT亚型mRNA在妊娠妇女子宫肌层组织和细胞中的表达。在培养的人子宫肌层细胞中测定Ca 2+离子载体A23187和体外拉伸（25%伸长，静态应变; Flexercell FX-4000张力系统）对NFAT表达的影响。人子宫肌层组织和培养细胞表达NFATc 1-c4 mRNA。培养细胞中NFATc 2基因表达在6 h牵张（11.5倍，P < 0.001，n = 6）和钙离子载体（A23187，5 μM）处理（20.6倍，P < 0.001，n = 6）中响应增加。在存在细胞内钙螯合剂BAPTA-AM（20 μM）的情况下，这种对拉伸的反应显著降低（90%，P < 0.001，n = 10）。这些数据表明，NFATc 2的表达是由细胞内钙离子和体外拉伸，并在人类子宫肌层细胞的拉伸反应是依赖于细胞内钙信号通路。我们的研究结果表明，NFATc 2在介导牵张诱导的基因表达本身的一个潜在的独特作用，并保证进一步探索有关的机制，促进子宫平滑肌生长在早期妊娠和/或劳动。
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. 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. 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). 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.