Activator Protein-2 Impairs the Invasion of a Human Extravillous Trophoblast Cell Line

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]
卷期号:150 (9): 4376-4385 被引量:27
标识
DOI:10.1210/en.2008-1645
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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