Molecular mechanism of the effect of angiopoietin-like protein 8 on the proliferation, invasion and migration of placental trophoblasts in preeclampsia.

Abstract

Preeclampsia (PE) is a pregnancy-specific systemic disorder characterized by various manifestations of organ dysfunction. Inadequate trophoblastic invasion of the uterine wall is involved in the pathogenesis of PE. Angiopoietin-like protein 8 (ANGPTL8) serves an important role in cardiovascular disease development and may have a potential effect on cell proliferation. In the present study, downregulation of ANGPTL8 promoted cell proliferation, decreased p21 expression, and increased the expression levels of cyclin-dependent kinase 2 and proliferating cell nuclear antigen in HTR8/SVneo cells. Silencing of ANGPTL8 led to significant acceleration in cell migration and invasion, and markedly enhanced the matrix metalloproteinase (MMP)-2 and MMP-9 expression levels. In addition, the protein expression levels of tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 were decreased in the group transfected with small interfering RNA (si)-ANGPTL8-1 as compared with those in the control and si-negative control groups. Taken together, these results indicated that ANGPTL8 downregulation promoted the proliferation, migration and invasion of trophoblast cells. Thus, ANGPTL8 suppresses the viability, proliferation, migration and invasion of trophoblast cells, and may be a potential therapeutic target for the clinical treatment of PE.