MXRA5 is decreased in preeclampsia and affects trophoblast cell invasion through the MAPK pathway.

Preeclampsia causes gestational failure in a significant number of women annually. Insufficient trophoblast cell invasion plays an essential role in preeclampsia pathogenesis. Matrix-remodeling associated 5 (MXRA5) is a proteoglycan involved in adhesion and matrix remodeling. This study sought to explore the role of MXRA5 in trophoblast cell invasion. Preeclamptic villi were obtained for the delineation of MXRA5 expression. Specific MXRA5 siRNA and pcDNA3.1/MXRA5 were used to manipulate MXRA5 expression in HTR-8/SVneo. Cell viability was determined by MTT and apoptosis by flow cytometry. Cell invasion was evaluated using Matrigel invasion assay. MXRA5 expression was lower in preeclamptic villi and cytotrophoblasts. Silencing MXRA5 expression in HTR-8/SVneo decreased cell viability and invasion, which were augmented by MXRA5 overexpression. Furthermore, MXRA5 modulated N-cadherin, E-cadherin, MMP-2, and MMP-9 expression through p38 MAPK and ERK1/2 signaling transduction. In addition, the expression of MXRA5 was influenced by exogenous TNF-α but not by IFN-γ. Overexpression of MXRA5 attenuated HTR-8/SVneo apoptosis induced by TNF-α. MXRA5 is downregulated in preeclamptic cytotrophoblasts and can regulate trophoblast cell invasion via the MAPK pathway.