Identifying genetic networks underlying myometrial transition to labor.
Identifying genetic networks underlying myometrial transition to labor.
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DOI：
10.1186/gb-2005-6-2-r12
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发表时间：
2005
期刊：
影响因子：
12.3
通讯作者：
Conklin BR
中科院分区：
文献类型：
--
作者：
Salomonis N;Cotte N;Zambon AC;Pollard KS;Vranizan K;Doniger SW;Dolganov G;Conklin BR
分娩开始时基因表达的时间过程揭示了与子宫肌肉激活相关的转录网络，并确定了预防早产的药物靶点。早产仍然是婴儿死亡的主要原因，但其原因在很大程度上是未知的。虽然已经确定了几个标记基因，但对潜在的全球基因表达模式和协调这些惊人变化的途径知之甚少。我们对小鼠子宫肌层在确定的生理状态下的9000多个基因进行了详细的时间过程研究：未怀孕、妊娠中期、妊娠晚期和产后。该数据集使我们能够识别出不同的基因表达模式，这些模式对应于子宫内膜“静止”、“术语激活”和“产后复旧”的阶段。利用最近开发的功能定位工具（HOPACH （hierarchical ordered partitioning and塌陷hybrid）和GenMAPP 2.0），我们已经确定了介导从静止到期激活转变的新的潜在转录调控基因网络。这些结果暗示肌层是内分泌激素（皮质醇和孕酮合成）和信号通路（环AMP和环GMP刺激）的重要调节剂，通过新的和先前相关的调节剂的转录上调来指导静止。通过长期激活，我们观察到细胞骨架重塑介质（中间丝）、细胞连接、转录调节因子的上调，以及平滑肌收缩信号负控制检查点的协同下调。这一分析为子宫收缩调节的多种平行机制提供了新的证据，并提出了调节子宫肌体转化和收缩的新的推测靶点。
A time course of gene expression at the onset of labor reveals transcriptional networks associated with activation of the uterine muscle and identifies targets for drugs to prevent premature labor. Early transition to labor remains a major cause of infant mortality, yet the causes are largely unknown. Although several marker genes have been identified, little is known about the underlying global gene expression patterns and pathways that orchestrate these striking changes. We performed a detailed time-course study of over 9,000 genes in mouse myometrium at defined physiological states: non-pregnant, mid-gestation, late gestation, and postpartum. This dataset allowed us to identify distinct patterns of gene expression that correspond to phases of myometrial 'quiescence', 'term activation', and 'postpartum involution'. Using recently developed functional mapping tools (HOPACH (hierarchical ordered partitioning and collapsing hybrid) and GenMAPP 2.0), we have identified new potential transcriptional regulatory gene networks mediating the transition from quiescence to term activation. These results implicate the myometrium as an essential regulator of endocrine hormone (cortisol and progesterone synthesis) and signaling pathways (cyclic AMP and cyclic GMP stimulation) that direct quiescence via the transcripitional upregulation of both novel and previously associated regulators. With term activation, we observe the upregulation of cytoskeletal remodeling mediators (intermediate filaments), cell junctions, transcriptional regulators, and the coordinate downregulation of negative control checkpoints of smooth muscle contractile signaling. This analysis provides new evidence of multiple parallel mechanisms of uterine contractile regulation and presents new putative targets for regulating myometrial transformation and contraction.
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影响因子：
--
作者：
Bethin, KE;Nagai, Y;Muglia, LJ
通讯作者：
Muglia, LJ
影响因子：
4
作者：
Aguan, K;Carvajal, JA;Weiner, CP
通讯作者：
Weiner, CP
影响因子：
12.3
作者：
Doniger SW;Salomonis N;Dahlquist KD;Vranizan K;Lawlor SC;Conklin BR
通讯作者：
Conklin BR
影响因子：
3.6
作者：
Havelock, OC;Keller, P;Word, RA
通讯作者：
Word, RA
影响因子：
3.4
作者：
Croy, BA;McBey, BA;vandenHeuvel, M
通讯作者：
vandenHeuvel, M