SFRP2 suppresses trophoblast cell migration by inhibiting the Wnt/β‑catenin pathway.

Abstract

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.