Department of Obstetrics and Gynaecology, Maternal and Child Health Hospital Affiliated to Anhui Medical University, Hefei 230001, China.
Department of Obstetrics and Gynaecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230031, China.
Biomolecules. 2024 Feb 29;14(3):293. doi: 10.3390/biom14030293.
The impaired invasion ability of trophoblast cells is related to the occurrence of preeclampsia (PE). We previously found that pregnancy-specific beta-1-glycoprotein 1 (PSG1) levels were decreased in the serum of individuals with early-onset preeclampsia (EOPE). This study investigated the effect of PSG1 on Orai1-mediated store-operated calcium entry (SOCE) and the Akt signaling pathway in human trophoblast cell migration. An enzyme-linked immunosorbent assay (ELISA) was used to determine the level of PSG1 in the serum of pregnant women with EOPE. The effects of PSG1 on trophoblast proliferation and migration were examined using cell counting kit-8 (CCK8) and wound healing experiments, respectively. The expression levels of Orai1, Akt, and phosphorylated Akt (p-Akt) were determined through Western blotting. The results confirmed that the serum PSG1 levels were lower in EOPE women than in healthy pregnant women. The PSG1 treatment upregulated the protein expression of Orai1 and p-Akt. The selective inhibitor of Orai1 (MRS1845) weakened the migration-promoting effect mediated by PSG1 via suppressing the Akt signaling pathway. Our findings revealed one of the mechanisms possibly involved in EOPE pathophysiology, which was that downregulated PSG1 may reduce the Orai1/Akt signaling pathway, thereby inhibiting trophoblast migration. PSG1 may serve as a potential target for the treatment and diagnosis of EOPE.
滋养细胞侵袭能力受损与子痫前期（PE）的发生有关。我们之前发现，早发型子痫前期（EOPE）患者血清中妊娠特异性β-1-糖蛋白 1（PSG1）水平降低。本研究探讨了 PSG1 对 Orai1 介导的钙库操纵性钙内流（SOCE）和人滋养细胞迁移中 Akt 信号通路的影响。酶联免疫吸附试验（ELISA）用于测定 EOPE 孕妇血清中的 PSG1 水平。通过细胞计数试剂盒-8（CCK8）和划痕愈合实验分别检测 PSG1 对滋养细胞增殖和迁移的影响。通过 Western blot 测定 Orai1、Akt 和磷酸化 Akt（p-Akt）的表达水平。结果证实，EOPE 妇女的血清 PSG1 水平低于健康孕妇。PSG1 处理上调了 Orai1 和 p-Akt 的蛋白表达。Orai1 的选择性抑制剂（MRS1845）通过抑制 Akt 信号通路削弱了 PSG1 介导的迁移促进作用。我们的研究结果揭示了 EOPE 病理生理学中可能涉及的机制之一，即下调的 PSG1 可能会减少 Orai1/Akt 信号通路，从而抑制滋养细胞迁移。PSG1 可能成为治疗和诊断 EOPE 的潜在靶点。
