1 Department of Obstetrics and Gynaecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
2 Key Laboratory of Birth Regulation and Control Technology of National Health and Family Planning Commission of China, Jinan, China.
Reprod Sci. 2019 Jan;26(1):35-43. doi: 10.1177/1933719118756773. Epub 2018 Feb 13.
Remodeling of maternal spiral artery after the implantation of embryo relies on tightly regulated trophoblast functions and is pivotal to ensure the success of pregnancy. Low-density lipoprotein receptor-related protein 6 (LRP6) is implicated in angiogenesis and several vascular diseases, but its function in trophoblast regulation is still not fully understood. We aimed to investigate the involvement of LRP6 in trophoblast functions during maternal spiral artery remodeling. HTR-8/SVneo cells, a trophoblast cell line, were employed to examine the impact of LRP6 knockdown on proliferation, apoptosis, and migration, as well as invasion and tube formation. Expression of matrix metalloproteinases (MMPs), angiogenic factors placental growth factor (PlGF), and vascular endothelial growth factor (VEGF), as well as activation of canonical Wnt/β-catenin signaling pathway, which was involved in artery remodeling process, was also analyzed. Lipoprotein receptor-related protein 6 knockdown suppressed proliferation, migration, invasion, and tube formation, as well as induced apoptosis in HTR-8/SVneo cells. In addition, LRP6 knockdown also significantly decreased expression of MMPs, PlGF, and VEGF and activation of Wnt/β-catenin signaling pathway. Lipoprotein receptor-related protein 6 might positively regulate the remodeling of the maternal artery through both endovascular formation and trophoblast invasion.
胚胎植入后母体螺旋动脉的重塑依赖于紧密调节的滋养细胞功能，这对于确保妊娠的成功至关重要。低密度脂蛋白受体相关蛋白 6（LRP6）参与血管生成和多种血管疾病，但它在滋养细胞调节中的功能尚不完全清楚。我们旨在研究 LRP6 在母体螺旋动脉重塑过程中对滋养细胞功能的影响。我们使用滋养细胞系 HTR-8/SVneo 细胞来研究 LRP6 敲低对增殖、凋亡、迁移以及侵袭和管形成的影响。还分析了基质金属蛋白酶（MMPs）、血管生成因子胎盘生长因子（PlGF）和血管内皮生长因子（VEGF）的表达，以及参与动脉重塑过程的经典 Wnt/β-catenin 信号通路的激活。LRP6 敲低抑制了 HTR-8/SVneo 细胞的增殖、迁移、侵袭和管形成，并诱导凋亡。此外，LRP6 敲低还显著降低了 MMPs、PlGF 和 VEGF 的表达以及 Wnt/β-catenin 信号通路的激活。LRP6 可能通过血管内形成和滋养细胞侵袭来正向调节母体动脉的重塑。
