Sphingosine-1-phosphate promotes extravillous trophoblast cell invasion by activating MEK/ERK/MMP-2 signaling pathways via S1P/S1PR1 axis activation.

Weiwei Yang,Zhifang Pan,Qinghua Li,Ashley Cowart

doi:10.1371/journal.pone.0106725

Weiwei Yang, Zhifang Pan + Show 2 more

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https://doi.org/10.1371/journal.pone.0106725

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Journal: PloS one	Publication Date: Sep 4, 2014
Citations: 69	License type: CC BY 4.0

Affiliation: Weifang Medical University

Abstract

Successful placentation depends on the proper invasion of extravillous trophoblast (EVT) cells into maternal tissues. Previous reports demonstrated that S1P receptors are expressed in the EVT cells and S1P could regulate migration and function of trophoblast cells via S1P receptors. However, little is known about roles of S1P in the invasion of EVT cells. Our study was performed to investigate S1P effect on the invasion of EVT cells. We used the extravillous trophoblast cell line HTR8/SVneo cells to evaluate the effect. In vitro invasion assay was employed to determine the invasion of HTR8/SVneo cells induced by S1P. MMP-2 enzyme activity and relative level in the supernatants of HTR8/SVneo was assessed by gelatin zymography and western blot. Based on the above, siRNA and specific inhibitors were used for the intervention and study of potential signal pathways, and Real-time qPCR and western blot were used to test the mRNA and protein level of potential signal targets. We found that S1P could promote HTR8/SVneo cell invasion and upregulates activity and level of MMP-2. The promotion requires activation of MEK-ERK and is dependent on the axis of S1P/S1PR1. Our investigation of S1P may provide new insights into the molecular mechanisms of EVT invasion.

Highlights

Invasion of maternal tissues at the maternal-fetal interface by extravillous trophoblast cells (EVT) plays important roles during the normal placentation and successful maintainment of human pregnancy [1,2]
To determine the effect of S1P on trophoblast cell behaviors, we examined cell proliferation and invasion in HTR8/SVneo cells that were treated with various concentrations of S1P
Enhanced invasion of S1P is mediated by MMP-2 Trophoblast cell invasion is often mediated by increased synthesis and activity of MMP-2 and MMP-9; An elevation of MMP-2 was observed in S1P-treated HTR8/SVneo cells using a gelatin zymography (Figure 2A) and western blot (Figure 2B)

Summary

Introduction

Invasion of maternal tissues at the maternal-fetal interface by extravillous trophoblast cells (EVT) plays important roles during the normal placentation and successful maintainment of human pregnancy [1,2]. Studies have shown that factors involved in trophoblast invasion regulation are associated with many gestation complications such as early pregnancy loss [6,7,8], preeclampsia [9,10] and fetal growth restriction [11]. It plays pivotal roles for successful gestation, the mechanisms underlying the regulation of EVT invasion are not clear, it is reported that the invasive capacities of EVT cells are regulated by several factors [12,13,14,15]

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