title: AP-2α suppresses invasion in BeWo cells by repression of matrix metalloproteinase-2 and -9 and up-regulation of E-cadherin.
abstract: Preeclampsia complicates 5-10% of pregnancies and is a leading cause of maternal/fetal morbidity and mortality. Although the cause is unknown, the reduced migration/invasion of extravillous trophoblasts is generally regarded as a key feature of preeclampsia genesis. The present study examined the expression of activator protein-2α (AP-2α), tissue inhibitor of metalloproteinase 2 (TIMP-2), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and E-cadherin in severe preeclamptic placentas and normal placentas using real-time PCR and immunohistochemistry. The expression levels of AP-2α, TIMP-2, and E-cadherin were elevated, while MMP-2 and MMP-9 levels were decreased in severe preeclamptic placentas when compared with normal placentas. To explore the underlying molecular mechanisms, BeWo cells were transfected with an AP-2α-expression construct as well as a siRNA against AP-2α. The over-expression of AP-2α decreased the invasive abilities of BeWo cells. AP-2α induction was followed by the induction of TIMP-2 and E-cadherin and a significant reduction of MMP-2 and MMP-9. Whereas in AP-2α-silencing BeWo cells, we observed the decreased expression of TIMP-2 and E-cadherin and the increased expression of MMP-2 and MMP-9. We presume that AP-2α may suppress trophoblast invasion by repression of MMP-2 and MMP-9 and up-regulation of E-cadherin, thus leading to shallow placentation in severe preeclampsia.
authors: Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China. zhangzhan27@gmail.com
authors: Zhan
authors: Z
authors: Zhang
authors: Ling
authors: L
authors: Zhang
authors: Liting
authors: L
authors: Jia
authors: Shihong
authors: S
authors: Cui
authors: Ying
authors: Y
authors: Shi
authors: Aimin
authors: A
authors: Chang
authors: Xianxu
authors: X
authors: Zeng
authors: Peng
authors: P
authors: Wang
mesh_terms: D000328:Adult; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050656:Transcription Factor AP-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
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