Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, Chengdu, Sichuan, PR China.
West China School of Public Health, Sichuan University, Sichuan, China.
Placenta. 2021 Jan 1;103:33-42. doi: 10.1016/j.placenta.2020.10.004. Epub 2020 Oct 6.
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.
子痫前期（PE）是产科医生面临的主要挑战。除了终止妊娠，目前尚无有效的方法可以阻止 PE 的发展。滋养细胞的生物学行为类似于癌细胞，这可能与 PE 的发病密切相关。巨噬细胞刺激蛋白（MSP）在癌症的发生和发展中的重要作用已经得到认可，而该蛋白在 PE 中的作用却鲜有报道。本研究旨在探讨 MSP 是否影响重度 PE（sPE），如果是，那么其作用机制是什么。收集患者信息、血液样本和/或胎盘组织。采用酶联免疫吸附试验（ELISA）测定血浆 MSP 浓度。分析血浆 MSP 浓度与临床特征的关系。采用免疫荧光法定位胎盘组织中的 MSP。采用 Western blot 和反转录定量聚合酶链反应（RT-qPCR）检测胎盘组织中 MSP 蛋白和 mRNA 的表达。通过慢病毒转染使滋养细胞系 HTR-8/SVneo 过表达或低表达 MSP，检测细胞的增殖、凋亡、迁移、侵袭和血管生成。sPE 患者的 MSP 表达下调，MSP 低表达抑制 HTR-8/SVneo 细胞的增殖、迁移、侵袭和血管生成。我们进一步验证了 MSP 通过 β-连环蛋白/ZEB1 信号通路影响滋养细胞的生物学行为。这些结果表明，sPE 患者，尤其是早发型 sPE 患者的血液和胎盘组织中 MSP 减少，导致滋养细胞侵袭减少，这在 PE 的发病机制中起重要作用。
