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

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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.

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Acknowledgments

This study was supported by the Key Laboratory of the Third Affiliated Hospital of Zhengzhou University in China. The authors gratefully acknowledge the faculty of Obstetric Institute and Department of Pathology for their technical assistance.

Conflict of interest

The authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Kangfuqian Street 7, Zhengzhou, 450052, China

    Zhan Zhang, Ling Zhang, Liting Jia, Ying Shi, Aimin Chang & Peng Wang

  2. Department of Gynaecology and Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Shihong Cui

  3. Department of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Xianxu Zeng

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  1. Zhan Zhang
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  2. Ling Zhang
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Correspondence to Ling Zhang.

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Zhang, Z., Zhang, L., Jia, L. et al. AP-2α suppresses invasion in BeWo cells by repression of matrix metalloproteinase-2 and -9 and up-regulation of E-cadherin. Mol Cell Biochem 381, 31–39 (2013). https://doi.org/10.1007/s11010-013-1685-8

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  • DOI: https://doi.org/10.1007/s11010-013-1685-8

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