Bone marrow stromal cell antigen 2(BST2) suppresses the migration and invasion of trophoblasts in preeclampsia by downregulating matrix metallopeptidase 2(MMP2)

Preeclampsia is a grievous pregnancy-related complication with an incidence of approximately 5∼7% in pregnant women. Placental abnormalities and decreased placental perfusion associated with impaired trophoblast invasion are early pathological findings of preeclampsia. BST2 is a multifunctional transmembrane protein that plays critical roles in physiological and pathological processes, but its impacts and mechanisms of action in preeclampsia are inadequately understood. The aim of this manuscript was to investigate the functional impacts of BST2 and MMP2 on the biological behavior of trophoblast cells in preeclampsia. The expression of these proteins and their genes was analyzed by qRT-PCR, western blotting and immunohistochemistry. The results showed that the expression of BST2 and MMP2 was significantly downregulated in preeclampsia. The migration and invasion capacities of HTR-8/SVneo and JAR cells with overexpression or knockdown of BST2 were detected by wound healing assay and Transwell assays. It was found that BST2 overexpression could up-regulate <i>MMP2</i> expression, and enhance the migration and invasion capacity of HTR-8/SVneo and JAR cells. BST2 knockdown could reverse these effects. MMP2 knockdown could downregulate the invasion capacity of HTR-8/SVneo cells, and MMP2 overexpression reversed these effects. Pearson correlation analysis demonstrated that the expression of MMP2 and BST2 were positively correlated. These results indicate that the downregulation of BST2 lowers MMP2 expression and restraint trophoblast functions, which probably explain its role in the pathogenesis of preeclampsia.

子痫前期（preeclampsia）是一种严重的妊娠相关并发症，在孕妇中的发病率约为5%~7%。胎盘异常及伴随滋养细胞侵袭受损的胎盘灌注降低，是子痫前期的早期病理特征。骨基质细胞抗原2（BST2）是一种多功能跨膜蛋白，在生理与病理过程中发挥关键作用，但其在子痫前期中的作用及分子机制尚未得到充分阐明。本研究旨在探讨BST2与基质金属蛋白酶2（MMP2）对子痫前期滋养细胞生物学行为的功能影响。研究通过实时荧光定量聚合酶链反应（qRT-PCR）、蛋白质印迹法（western blotting）及免疫组织化学技术，对上述两种蛋白及其编码基因的表达水平进行了检测分析。结果显示，子痫前期样本中BST2与MMP2的表达水平均显著下调。本研究采用划痕愈合实验与Transwell实验，检测了过表达或敲低BST2的HTR-8/SVneo及JAR细胞的迁移与侵袭能力。研究发现，BST2过表达可上调MMP2的表达，并增强HTR-8/SVneo与JAR细胞的迁移及侵袭能力；而敲低BST2则可逆转上述效应。敲低MMP2可降低HTR-8/SVneo细胞的侵袭能力，而过表达MMP2则可逆转这一现象。皮尔逊相关分析结果表明，MMP2与BST2的表达水平呈显著正相关。上述结果表明，BST2表达下调会降低MMP2的表达并抑制滋养细胞功能，这或许可阐释BST2在子痫前期发病过程中的作用机制。