G-protein-coupled receptor 30 mediates the effects of estrogen on endothelial cell tube formation in vitro.
G-protein-coupled receptor 30 mediates the effects of estrogen on endothelial cell tube formation in vitro.
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G蛋白偶联受体30介导雌激素对体外内皮细胞管形成的影响
DOI：
10.3892/ijmm.2017.2957
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发表时间：
2017-06
影响因子：
5.4
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Zhou L;Chen H;Mao X;Qi H;Baker PN;Zhang H
胎盘是母亲和胎儿之间的交换器官。这个器官的功能不足与许多妊娠障碍有关。胎盘发育过程中的缺氧和氧化应激可诱导内皮功能障碍，导致胎盘灌注减少。在怀孕期间，雌激素的水平会增加。据报道，患有先兆子痫的女性雌激素水平降低。然而，雌激素是否参与胎盘血管生成仍不清楚。在这项研究中，我们的目的是研究雌激素对内皮细胞管形成的影响，并阐明其潜在的机制。为此，在缺氧/复氧（H/R）条件下，用17-β-雌二醇培养人脐静脉内皮细胞（HUVECs）。测量内皮细胞上管状结构的总管长。采用免疫印迹法和免疫组化法检测17 β雌二醇处理后H/R条件下内皮细胞G蛋白偶联受体30（GPR30）、内皮型一氧化氮合酶（eNOS）和Akt的表达水平。我们发现内皮细胞上的管状结构的总管道长度显著减少。17-β-雌二醇治疗可逆转这种降低。17-β-雌二醇处理后，内皮细胞GPR30的表达明显增加。17-β-雌二醇处理后，内皮细胞eNOS和Akt水平明显升高。PI 3 K/Akt抑制剂渥曼青霉素（wortmannin）可抑制eNOS的激活。因此，我们的数据表明，雌激素防止由H/R诱导的内皮细胞管形成的失败。GPR30通过激活内皮细胞中的eNOS和Akt在这些保护作用中起重要作用。我们的数据表明，雌激素水平的增加对胎盘血管生成很重要。
The placenta is the exchange organ between the mother and the fetus. The inadequate function of this organ is associated with a number of pregnancy disorders. Hypoxia and oxidative stress during placental development may induce endothelial dysfunction, resulting in the reduction in the perfusion of the placenta. During pregnancy, the levels of estrogen are increased. Decreased estrogen levels have been reported in women with preeclampsia. However, whether estrogen is involved in placental angiogenesis remains unclear. In this study, we aimed to investigate the effects of estrogen on endothelial cell tube formation and to elucidate the underlying mechanisms. For this purpose, human umbilical vein endothelial cells (HUVECs) were cultured with 17-β-estradiol under conditions of hypoxia/reoxygenation (H/R). The total pipe length of the tube-like structure on endothelial cells was measured. The expression levels of G-protein-coupled receptor 30 (GPR30) and endothelial nitric oxide synthase (eNOS) and Akt were also measured in the endothelial cells following treatment with 17-β-estradiol under H/R conditions by western blot analysis and immunostaining. We found that the total pipe length of the tube-like structure on endothelial cells was significantly reduced. This reduction was reversed by treatment with 17-β-estradiol. The expression of GPR30 in endothelial cells was significantly increased following treatment with 17-β-estradiol under H/R conditions. Furthermore, the levels of eNOS and Akt in endothelial cells were also significantly increased following treatment with 17-β-estradiol under H/R conditions. The activation of eNOS was inhibited by wortmannin, an inhibitor of PI3K/Akt. Our data thus demonstrate that estrogen prevents the failure of endothelial cell tube formation induced by H/R. GPR30 plays an important role in these protective effects through the activation of eNOS and Akt in endothelial cells. Our data suggest that increased levels of estrogen are important for placental angiogenesis.