Activin-A in myometrium: Characterization of the actions on myometrial cells

Activin-A in myometrium: Characterization of the actions on myometrial cells
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DOI:
10.1210/en.2007-0692
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发表时间:
2008-05-01
期刊:
影响因子:
4.8
通讯作者:
Vale, Wylie
Vale, Wylie
中科院分区:
医学2区
文献类型:
--
作者:
Ciarmela, Pasquapina;Wiater, Ezra;Vale, Wylie

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激活素是一种多效性生长因子,具有广泛的组织分布模式,包括生殖组织。虽然激活素在性腺和子宫组织中的直接作用已经被描述,但在子宫肌层中的作用还没有被定义。在这项研究中,我们表征了子宫组织和子宫肌层细胞系对ActivinA的反应性。子宫组织和两个子宫肌层细胞系PHM1(妊娠人子宫肌层细胞)和hTERT HM(端粒酶逆转录酶感染的人子宫肌层细胞)对激活素-A有反应,通过Smad-2的磷酸化检测。这些细胞系表达完整的激活素受体,以及激活素β(A)亚单位和卵泡抑素。激活素抑制PHM1和人端粒酶逆转录酶感染的人子宫肌层细胞系的增殖,在PHM1中观察到更广泛的生长抑制。在PHM1中,激活素-A降低催产素受体和HoxA-10mRNA的表达,但不改变总孕酮受体、环氧合酶-2(COX-2)和连接蛋白43的mRNA表达水平。此外,用激活素-A处理PHM1肌层细胞可减弱催产素和血栓素A2诱导的细胞内钙离子积聚。总之,子宫肌层细胞对激活素敏感,激活素-A可以调节肌层细胞的功能。
Activin is a pleiotropic growth factor with a broad pattern of tissue distribution that includes reproductive tissues. Although direct actions of activin have been described in gonadal and uterine tissues, actions in the myometrium have not been defined. In this study we have characterized the responsiveness of uterine tissue and myometrial cell lines to activinA. Uterine tissue and two myometrial cell lines, PHM1 ( pregnant human myometrial 1) and hTERT HM ( telomerase reverse transcriptase- infected human myometrial) respond to activin- A as measured by phosphorylation of Smad- 2. Those cell lines express a full complement of activin receptors, as well as activin beta(A) subunit and follistatin. Activin inhibited proliferation of PHM1 and human telomerase reverse transcriptase-infected human myometrial cell line cells, with more extensive growth inhibition observed in PHM1s. In PHM1s, activin-A decreased oxytocin receptor and HoxA-10 mRNA expression but did not alter total progesterone receptor, cyclooxygenase-2 ( Cox-2), and connexin 43 mRNA expression levels. Furthermore, treatment of PHM1 myometrial cells with activin-A attenuated oxytocin and thromboxaneA2 induced intracellular Ca2+ accumulation. In conclusion, myometrial cells are activin sensitive, and activin-A can regulate myometrial cell functions.