AP-2 alpha suppresses invasion in BeWo cells by repression of matrix metalloproteinase-2 and-9 and up-regulation of E-cadherin

作者：Zhang Zhan; Zhang Ling^*; Jia Liting; Cui Shihong; Shi Ying; Chang Aimin; Zeng Xianxu; Wang Peng

来源：Molecular and Cellular Biochemistry, 2013, 381(1-2): 31-39.

DOI：10.1007/s11010-013-1685-8

• Preeclampsia
• AP-2 alpha
• Cell invasion
• BeWo cells
• Trophoblast

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-2 alpha (AP-2 alpha), 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-2 alpha, 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-2 alpha-expression construct as well as a siRNA against AP-2 alpha. The over-expression of AP-2 alpha decreased the invasive abilities of BeWo cells. AP-2 alpha 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-2 alpha-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-2 alpha 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.

• 出版日期2013-9
• 单位郑州大学