一项研究发现，称为微RNA的小片RNA可能通过促使子宫在分娩期间收缩而在子宫组织中起基因开关的作用。科学家长久以来知道诸如黄体酮和催产素等激素在怀孕和分娩中起到了重要作用。但是这种肌肉子宫壁（子宫肌层）变形――也就是从静止的组织变成收缩的组织――的信号传导机制尚不很清楚。Carole R. Mendelson及其同事使用基因表达分析发现了miR-200微RNA及其目标蛋白质ZEB1 和ZEB2参与的一个反馈信号传导回路，它们帮助子宫肌层对分娩诱导信号作出反应而收缩。
这组作者报告说，尽管当子宫收缩的时候小鼠和人的子宫肌层的这种微RNA的浓度上升，ZEB1和ZEB2的浓度下降。在怀孕期间，高浓度的循环的黄体酮帮助增加了子宫肌层的ZEB1浓度，而接近足月的时候，小鼠和人的子宫ZEB1浓度急剧下降。此外，在实验室中生长的子宫肌层细胞中，ZEB1和ZEB2降低了与子宫收缩有关的蛋白质的合成，阻滞了催产素诱导的子宫肌肉收缩。这组作者说，这些发现为子宫收缩的机制提供了解释，并且为预防新生儿死亡的主要原因早产提供了见解。
生物谷推荐英文摘要：
PNAS doi: 10.1073/pnas.1008301107
miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor
Nora E. Renthala,b, Chien-Cheng Chena,b, Koriand'r C. Williamsa,b, Robert D. Gerardc, Janine Prange-Kield, and Carole R. Mendelsona,b,e,1
Departments of aBiochemistry, eObstetrics and Gynecology, cInternal Medicine, and dCell Biology, bNorth Texas March of Dimes Birth Defects Center, University of Texas Southwestern Medical Center, Dallas, TX 75390
Throughout most of pregnancy, uterine quiescence is maintained by increased progesterone receptor (PR) transcriptional activity, whereas spontaneous labor is initiated/facilitated by a concerted series of biochemical events that activate inflammatory pathways and have a negative impact on PR function. In this study, we uncovered a previously undescribed regulatory pathway whereby micro-RNAs (miRNAs) serve as hormonally modulated and conserved mediators of contraction-associated genes in the pregnant uterus in the mouse and human. Using miRNA and gene expression microarray analyses of uterine tissues, we identified a conserved family of miRNAs, the miR-200 family, that is highly induced at term in both mice and humans as well as two coordinately down-regulated targets, zinc finger E-box binding homeobox proteins ZEB1 and ZEB2, which act as transcriptional repressors. We also observed up-regulation of the miR-200 family and down-regulation of ZEB1 and ZEB2 in two different mouse models of preterm labor. We further demonstrated that ZEB1 is directly up-regulated by the action of progesterone (P4)/PR at the ZEB1 promoter. Excitingly, we observed that ZEB1 and ZEB2 inhibit expression of the contraction-associated genes, oxytocin receptor and connexin-43, and block oxytocin-induced contractility in human myometrial cells. Together, these findings implicate the miR-200 family and their targets, ZEB1 and ZEB2, as unique P4/PR-mediated regulators of uterine quiescence and contractility during pregnancy and labor and shed light on the molecular mechanisms involved in preterm birth.
