内分泌学
内科学
激活剂(遗传学)
滋养层
细胞培养
生物
细胞生物学
化学
医学
怀孕
胎儿
受体
遗传学
胎盘
作者
Tomomi Kotani,Akira Iwase,Kazuhiko Ino,Seiji Sumigama,Eiko Yamamoto,Hiromi Hayakawa,Tetsuo Nagasaka,Atsuo Itakura,Seiji Nomura,Fumitaka Kikkawa
出处
期刊:Endocrinology
[Oxford University Press]
日期:2009-05-14
卷期号:150 (9): 4376-4385
被引量:27
摘要
Abstract The reduced migration/invasion of extravillous trophoblasts (EVTs) is a key feature of the genesis of preeclampsia. We and others previously reported that transcriptional factors activator protein-2 (AP-2) α and AP-2γ act as suppressors of tumor invasion. The present study examined the expressions of AP-2α and AP-2γ in preeclamptic placenta vs. control placenta and investigated their effect on the function of EVTs. The expressions of AP-2α and AP-2γ were elevated in the preeclamptic placentas in comparison with the gestational age-matched control placentas. Their expressions also increased in EVTs of the preeclamptic placentas. Thereafter, we transfected AP-2α or AP-2γ into human EVT cell line, HTR-8/SVneo. The overexpression of AP-2α or AP-2γ decreased the migratory and invasive abilities in HTR-8/SVneo cells. This was followed by the reduction of protease activated receptor-1 and matrix metalloproteinases and a significant induction of plasminogen activator inhibitor-1 and the tissue inhibitor of metalloproteinase-1. AP-2α and AP-2γ were weakly expressed in the cultured EVTs and HTR-8/SVneo cells, whereas they were induced by TNF-α, which increases in preeclamptic placenta and impairs trophoblast invasion. In the presence of TNF-α, the invasion of the HTR-8/SVneo cells was partially restored by a blocking of AP-2 induction using small interfering RNA of AP-2. The present data suggest that AP-2 may suppress trophoblast migration and invasion, thus leading to a shallow placentation in preeclampsia.
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