Application of a functional genomics approach to identify differentially expressed genes in human myometrium during pregnancy and labour

Application of a functional genomics approach to identify differentially expressed genes in human myometrium during pregnancy and labour
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DOI:
10.1093/molehr/6.12.1141
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发表时间:
2000-12-01
影响因子:
4
通讯作者:
Weiner, CP
Weiner, CP
中科院分区:
医学2区
文献类型:
--
作者:
Aguan, K;Carvajal, JA;Weiner, CP

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在怀孕期间调节子宫松弛和收缩的分子机制尚不清楚。在本研究中,我们首次使用功能基因组学方法,应用基因阵列技术鉴定了参与妊娠期间子宫静止和收缩调节的新的候选基因。这种方法的目的是获得基因转录物的表达谱的分子快照,作为调节子宫肌静息的时间依赖过程的函数。利用这种方法,我们发现了几个基因,它们在人子宫肌层中的表达随着分娩的开始而改变。例如,产程中胰岛素样生长因子(IGF)-II、钙颗粒蛋白A和B、g蛋白偶联受体的表达降低,而与未产程相比,产程中IGF结合蛋白、Ca2+/CaM结合蛋白激酶C底物和血管紧张素转换酶的表达升高。差异表达的基因包括几个在子宫肌静息中的作用尚不清楚的基因,尽管它们已被报道调节血管平滑肌张力。我们的研究结果说明了功能基因组学方法在识别大量新的和潜在的重要基因介导子宫平滑肌收缩活动方面比单基因分析具有优势。
The molecular mechanisms regulating uterine relaxation and contraction during pregnancy are poorly understood. In the present study, we used for the first time a functional genomics approach applying gene array technology to identify novel candidate genes involved in the regulation of uterine quiescence and contractility during pregnancy. The purpose of this approach was to obtain a molecular snapshot of the expression profile of gene transcripts as a function of the time dependent process regulating myometrial quiescence. Using this approach, we found several genes whose expression in human myometrium was altered with the onset of labour. For example, the expression of insulin-like growth factor (IGF)-II, calgranulin A and B, and G-protein coupled receptor were decreased while the expression of IGF-binding proteins, Ca2+/CaM binding protein kinase C substrate, and angiotensin converting enzyme were increased in the labouring, compared with non-labouring, pregnant myometrium. The differentially-expressed genes include several genes whose roles in myometrial quiescence are yet to be understood, although they have been reported to regulate vascular smooth muscle tone. Our findings illustrate the advantage of a functional genomics approach over a single gene analysis in identifying a large number of novel and potentially important genes mediating uterine smooth muscle contractile activity.