Department of Obstetrics, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, P.R. China.
School of Clinical Medicine, Hainan Medical University, Haikou, Hainan 571199, P.R. China.
Mol Med Rep. 2024 Apr;29(4). doi: 10.3892/mmr.2024.13190. Epub 2024 Mar 1.
The present study investigates the role of Secreted Frizzled‑Related Protein 2 (SFRP2) in trophoblast cells, a key factor in preeclampsia (PE) progression. Elevated levels of Secreted Frizzled‑Related Protein 1/3/4/5 (SFRP1/3/4/5) are associated with PE, but the role of SFRP2 is unclear. We analyzed SFRP2 expression in PE placental tissue using the GSE10588 dataset and overexpressed SFRP2 in JEG‑3 cells via lentiviral transfection. The viability, migration, apoptosis, and proliferation of SFRP2‑overexpressing JEG‑3 cells were assessed using Cell Counting Kit‑8, Transwell assays, flow cytometry, and EdU staining. Additionally, we evaluated the impact of SFRP2 overexpression on key proteins in the Wnt/β‑catenin pathway and apoptosis markers (Bax, cleaved‑caspase 3, BCL‑2, MMP9, E‑cadherin, Wnt3a, Axin2, CyclinD1, c‑Myc, p‑β‑catenin, β‑catenin, phosphorylated Glycogen Synthase Kinase 3 beta (p‑GSK3β), and GSK3β) through western blotting. Results showed high SFRP2 mRNA and protein expression in PE placenta and JEG‑3 cells post‑transfection. SFRP2 overexpression significantly reduced JEG‑3 cell viability, proliferation, and migration, while increasing apoptosis. It also altered expression levels of Wnt pathway proteins, suggesting SFRP2's potential as a therapeutic target for PE by inhibiting trophoblast cell migration through the Wnt/β‑catenin signaling cascade.
本研究探讨了分泌型卷曲相关蛋白 2（SFRP2）在胎盘滋养细胞中的作用，这是子痫前期（PE）进展的关键因素。分泌型卷曲相关蛋白 1/3/4/5（SFRP1/3/4/5）水平升高与 PE 相关，但 SFRP2 的作用尚不清楚。我们使用 GSE10588 数据集分析了 PE 胎盘组织中的 SFRP2 表达，并通过慢病毒转染在 JEG-3 细胞中过表达 SFRP2。使用细胞计数试剂盒-8、Transwell 分析、流式细胞术和 EdU 染色评估 SFRP2 过表达对 JEG-3 细胞活力、迁移、凋亡和增殖的影响。此外，我们还通过 Western blot 评估了 SFRP2 过表达对 Wnt/β-catenin 通路关键蛋白和凋亡标志物（Bax、cleaved-caspase 3、BCL-2、MMP9、E-钙粘蛋白、Wnt3a、Axin2、CyclinD1、c-Myc、p-β-catenin、β-catenin、磷酸化糖原合成酶激酶 3β（p-GSK3β）和 GSK3β）的影响。结果显示，PE 胎盘和转染后的 JEG-3 细胞中 SFRP2 mRNA 和蛋白表达水平较高。SFRP2 过表达显著降低 JEG-3 细胞活力、增殖和迁移，同时增加凋亡。它还改变了 Wnt 通路蛋白的表达水平，表明 SFRP2 通过抑制 Wnt/β-catenin 信号级联促进滋养细胞迁移，具有作为 PE 治疗靶点的潜力。
