Macrophage-stimulating protein is decreased in severe preeclampsia and regulates the biological behavior of HTR-8/SVneo trophoblast cells

Abstract

Preeclampsia (PE) is a major challenge for obstetricians. There is no effective way to block the development of PE other than terminating the pregnancy. The biological behavior of trophoblast cells, which are similar to cancer cells, may be closely related to the onset of PE. The vital role of macrophage-stimulating protein (MSP) in the development and progression of cancer has been recognized, while a role for this protein in PE has rarely been reported. This study aimed to explore whether MSP affects severe PE (sPE) and, if so, to characterize the mechanism. Patient information, blood samples and/or placental tissues were collected. An enzyme-linked immunosorbent assay (ELISA) was used to determine the plasma MSP concentration. The relationships between the plasma MSP concentration and clinical characteristics were analyzed. Immunofluorescence was performed to localize MSP in placental tissues. Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to determine MSP protein and mRNA expression in placental tissues. MSP was overexpressed or underexpressed in the trophoblastic cell line HTR-8/SVneo by lentiviral transfection and the proliferation, apoptosis, migration, invasion and angiogenesis of cells were detected. MSP was downregulated in sPE, and the underexpression of MSP inhibited HTR-8/SVneo cell proliferation, migration, invasion and angiogenesis. We further verified that MSP affects the biological behavior of trophoblast cells through the β-catenin/ZEB1 signaling pathway. These results suggest that decreased MSP in the blood and placental tissues of patients with sPE, especially those with early-onset sPE, leads to reduced trophoblast cell invasion, which plays an important role in the pathogenesis of PE.