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

Abstract

ABSTRACT 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 MMP2 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.