一項研究發(fā)現(xiàn),，稱為微RNA的小片RNA可能通過促使子宮在分娩期間收縮而在子宮組織中起基因開關(guān)的作用,?？茖W家長久以來知道諸如黃體酮和催產(chǎn)素等激素在懷孕和分娩中起到了重要作用,。但是這種肌肉子宮壁（子宮肌層）變形——也就是從靜止的組織變成收縮的組織——的信號傳導(dǎo)機制尚不很清楚,。Carole R. Mendelson及其同事使用基因表達分析發(fā)現(xiàn)了miR-200微RNA及其目標蛋白質(zhì)ZEB1 和ZEB2參與的一個反饋信號傳導(dǎo)回路，它們幫助子宮肌層對分娩誘導(dǎo)信號作出反應(yīng)而收縮,。
這組作者報告說,，盡管當子宮收縮的時候小鼠和人的子宮肌層的這種微RNA的濃度上升，ZEB1和ZEB2的濃度下降,。在懷孕期間,，高濃度的循環(huán)的黃體酮幫助增加了子宮肌層的ZEB1濃度，而接近足月的時候,，小鼠和人的子宮ZEB1濃度急劇下降,。此外，在實驗室中生長的子宮肌層細胞中,，ZEB1和ZEB2降低了與子宮收縮有關(guān)的蛋白質(zhì)的合成,，阻滯了催產(chǎn)素誘導(dǎo)的子宮肌肉收縮。這組作者說,，這些發(fā)現(xiàn)為子宮收縮的機制提供了解釋,，并且為預(yù)防新生兒死亡的主要原因早產(chǎn)提供了見解。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
