The Loss of Endoglin Promotes the Invasion of Extravillous Trophoblasts
The Loss of Endoglin Promotes the Invasion of Extravillous Trophoblasts
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DOI：
10.1210/en.2011-1088
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发表时间：
2011-11-01
期刊：
影响因子：
4.8
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
--
作者：
Mano, Yukio;Kotani, Tomomi;Kikkawa, Fumitaka
内皮糖蛋白是TGF-β的辅助受体，其在合体滋养层中表达。已经观察到可溶性形式的内皮糖蛋白（sEng）在先兆子痫患者的血清中增加。几项研究表明，内皮糖蛋白参与了癌症的侵袭。然而，内皮糖蛋白在绒毛外滋养层细胞（EVT）中的作用，这具有侵袭性表型，仍然未知。本研究旨在探讨内皮糖蛋白在人EVT中的表达及其作用。我们发现endoglin主要表达在细胞滋养层细胞内的细胞柱在早期妊娠和EVT的表达减少免疫组化和免疫细胞化学。用半定量RT-PCR检测到，在人EVT细胞系HTR-8/SVneo中，经TGF-β 1和TGF-β 3处理后，endoglin的表达显著增加。为了研究内皮糖蛋白在EVT中的作用，通过慢病毒短发夹RNA转染HTR-8/SVneo细胞来进行内皮糖蛋白的稳定敲除。虽然增殖没有受到影响，HTR-8/SVneo细胞的运动性和侵袭性显着增加的敲低endoglin。内皮糖蛋白基因敲低细胞尿激酶型纤溶酶原激活物的mRNA表达和分泌均显著增加。HTR-8/SVneo中sEng的分泌非常低，并且用10 ng/ml sEng处理endoglin敲低的细胞对其侵袭性没有影响。因此，sEng的抑制不参与内皮糖蛋白敲低细胞的侵袭性增加。结果提示，EVT通过降低内皮素的表达，增强了细胞的侵袭功能。（内分泌学152：4386-4394，2011）
Endoglin is a coreceptor for TGF-beta, which is expressed in syncytiotrophoblasts. The soluble form of endoglin (sEng) has been observed to increase in the serum of preeclamptic patients. Several studies have shown that endoglin is involved in cancer invasion. However, the role of endoglin in extravillous trophoblasts (EVT), which have an invasive phenotype, remains unknown. The present study was designed to investigate the expression and role of endoglin in human EVT. We found that endoglin was mainly expressed on cytotrophoblasts within the cell column during the first trimester and its expression decreased in the EVT by immunohistochemistry and immunocytochemistry. The expression of endoglin significantly increased after treatment with TGF-beta 1 and TGF-beta 3 in the human EVT cell line, HTR-8/SVneo, as detected by semiquantitative RT-PCR. To investigate the role of endoglin in EVT, the stable knockdown of endoglin was performed by lentiviral short hairpin RNA transfection into the HTR-8/SVneo cells. Although proliferation was not affected, the motility and invasiveness of the HTR-8/SVneo cells significantly increased by the knockdown of endoglin. Both the mRNA expression and secretion of urokinase-type plasminogen activator significantly increased in endoglin knockdown cells. The secretion of sEng was very low in HTR-8/SVneo, and the treatment of endoglin knockdown cells with 10 ng/ml sEng had no effect on their invasiveness. Therefore, the suppression of sEng was not involved in the increased invasiveness of endoglin knockdown cells. These results suggested that EVT increased their invasive function as a result of decreasing expression of transmembrane endoglin. (Endocrinology 152: 4386-4394, 2011)