Angiotensin II mimics the hypoxic effect on regulating trophoblast proliferation and differentiation in human placental explant cultures
Angiotensin II mimics the hypoxic effect on regulating trophoblast proliferation and differentiation in human placental explant cultures
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DOI：
10.1016/j.lfs.2007.10.017
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发表时间：
2008-01-02
期刊：
影响因子：
6.1
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
--
作者：
Araki-Taguchi, Masako;Nomura, Seiji;Kikkawa, Fumitaka
调节细胞滋养层细胞向绒毛外滋养层细胞的分化是成功妊娠的关键。以前的研究主要集中在促进分化的因素上，而除了缺氧之外的抑制调节因子的文献较少。在这项研究中，为了验证我们的假设，血管紧张素II(Ang II)将抑制EVT分化，我们利用人早孕绒毛组织块培养，观察了Ang II对滋养层细胞生长的影响以及与滋养层细胞增殖和侵袭相关的分子的表达。Ang II可增加EVT的生长和细胞柱中的细胞数。经血管紧张素Ⅱ处理的组织块表现出EVT中Ki67和整合素α5免疫反应增强，条件培养液中基质金属蛋白酶2活性增强，α1整合素免疫反应降低，这与EVT的增殖表型特征相一致。Ang II的上述作用与缺氧组(3%02)相似。Ang II刺激缺氧诱导因子-1α在mRNA和蛋白水平的表达，并促进纤溶酶原激活物抑制物-1(PAI-1)的表达。本文提供的数据提示Ang II可能在阻碍滋养层细胞分化为侵袭性表型方面发挥作用，这可能与子痫前期胎盘的浅表侵袭性有关。(C)2007 Elsevier Inc.保留所有权利。
Regulation of cytotrophoblast differentiation toward extravillous trophoblasts (EVTs) is critical for establishing successful pregnancy. Previous studies have focused primarily on the factors promoting the differentiation, while inhibitory regulators except hypoxia have been less documented. In this study, to test our hypothesis that angiotensin II (Ang II) would inhibit EVT differentiation, we investigated the effects of Ang II on trophoblast outgrowth and the expression of molecules associated with the proliferation and invasion of trophoblasts using human first trimester villous explant cultures. Ang II increased EVT outgrowth and the number of cells in cell columns. Moreover, Ang II-treated explants exhibited increased Ki67 and integrin alpha 5 immunoreactivity in EVTs as well as matrix metalloproteinase-2 activity in the conditioned media, and decreased alpha 1 integrin immunoreactivity, which are compatible with the features of the proliferative phenotype EVTs. These effects of Ang II were similar to those of hypoxia (3% 02). Ang II stimulated the expression of hypoxia inducible factor-1 alpha at both mRNA and protein levels, and also enhanced the expression of plasminogen activator inhibitor-1 (PAI-1). Data presented herein suggest a possible role for Ang II in impairing trophoblast differentiation toward an invasive phenotype, which might be associated with shallow invasion in preeclamptic placentas. (C) 2007 Elsevier Inc. All rights reserved.