Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36# Sanhao Street, Shenyang, 110004, China.
Commun Biol. 2024 Nov 1;7(1):1427. doi: 10.1038/s42003-024-07149-7.
Preeclampsia (PE) is a common pregnancy disorder characterized by hypertension and proteinuria. Trophoblast behavior severely affect PE progression. Transcription factor Forkhead box protein P2 (FOXP2) was involved in cell migration and invasion, but its role in PE progression remains unknown. Laminin subunit alpha 4 (LAMA4) was predicted as a downstream gene of FOXP2 and related to PE. Thus, we supposed that FOXP2 might regulate PE by regulating LAMA4. We found the decreased FOXP2 expression in patients with PE compared with healthy pregnant women. The rat model of PE was induced by L-NAME oral gavage. FOXP2 overexpression lowered systolic and diastolic blood pressure and restored pathological changes of rats with PE. Trophoblasts under the hypoxia/reoxygenation (H/R) treatment were used to mimic PE in vitro. The results revealed that FOXP2 overexpression inhibited apoptosis but promoted migration, invasion, and angiogenesis of H/R-treated trophoblasts. Dual luciferase and chromatin immunoprecipitation-polymerase chain reaction assays confirmed that FOXP2 transcriptionally upregulated the LAMA4 expression in trophoblasts. LAMA4 knockdown reversed the migration and invasion-promoting role of FOXP2 overexpression in trophoblasts with H/R treatment. Collectively, our findings suggest that the FOXP2/LAMA4 axis regulates PE by suppressing trophoblast apoptosis and promoting its migration, invasion, and angiogenesis.
子痫前期（PE）是一种常见的妊娠疾病，其特征为高血压和蛋白尿。滋养细胞行为严重影响 PE 的进展。转录因子叉头框蛋白 P2（FOXP2）参与细胞迁移和侵袭，但它在 PE 进展中的作用尚不清楚。层粘连蛋白亚基 alpha 4（LAMA4）被预测为 FOXP2 的下游基因，与 PE 相关。因此，我们假设 FOXP2 可能通过调节 LAMA4 来调节 PE。我们发现与健康孕妇相比，PE 患者的 FOXP2 表达降低。通过 L-NAME 口服灌胃诱导 PE 大鼠模型。FOXP2 的过表达降低了收缩压和舒张压，并恢复了 PE 大鼠的病理变化。缺氧/复氧（H/R）处理的滋养细胞用于体外模拟 PE。结果表明，FOXP2 的过表达抑制了 H/R 处理的滋养细胞凋亡，但促进了其迁移、侵袭和血管生成。双荧光素酶和染色质免疫沉淀-聚合酶链反应实验证实，FOXP2 在转录水平上上调了滋养细胞中 LAMA4 的表达。LAMA4 敲低逆转了 FOXP2 过表达在 H/R 处理的滋养细胞中促进迁移和侵袭的作用。综上所述，我们的研究结果表明，FOXP2/LAMA4 轴通过抑制滋养细胞凋亡和促进其迁移、侵袭和血管生成来调节 PE。
