Luo Q, Liu X, Zheng Y, Zhao Y, Zhu J, Zou L
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Placenta. 2015 May;36(5):567-74. doi: 10.1016/j.placenta.2015.02.009. Epub 2015 Feb 21.
Maternal spiral artery remodeling after embryo implantation is a crucial process for successful pregnancy and rely on well-controlled trophoblast functions. Ephrin-B2 is found to be of great importance in various cell functions in both benign human tissue and tumors. However, its role in the regulation of trophoblast remains unknown. This study is conducted to investigate the role of ephrin-B2-induced trophoblast functions related to artery remodeling.
Trophoblast cell line HTR-8/SVneo was used to investigate the effects of ephrin-B2 inhibition on cell proliferation, apoptosis, migration, invasion and tube formation. Placental-decidual co-culture (PDC) system was conducted to verify ephrin-B2-induced trophoblast functions ex vivo. Factors involving in artery remodeling process, such as matrix metalloproteinases (MMPs), placental growth factors (PlGF) and vascular endothelial growth factor (VEGF) were tested at transcriptional level.
Inhibition of ephrin-B2 suppressed cell proliferation and induced cell apoptosis in HTR-8/SVneo cells. Down-regulation of ephrin-B2 impaired migration/invasion capabilities of HTR-8/SVneo cells and significantly decreased gene expression of MMPs. Also, a worse tube formation and a decrease in gene expression of PlGF was observed after down-regulation of ephrin-B2. However gene expression of VEGF-A did not show significantly statistical difference. These effects were further confirmed by PDC system showing an inadequate trophoblast invasion and spiral artery remodeling.
Ephrin-B2 might be act as a positive regulator in maternal artery remodeling via both trophoblast invasion and endovascular formation.
胚胎着床后母体螺旋动脉重塑是成功妊娠的关键过程，依赖于严格调控的滋养层细胞功能。已发现 Ephrin-B2 在人类良性组织和肿瘤的各种细胞功能中具有重要作用。然而，其在滋养层细胞调控中的作用尚不清楚。本研究旨在探讨 Ephrin-B2 诱导的与动脉重塑相关的滋养层细胞功能的作用。
使用滋养层细胞系 HTR-8/SVneo 研究 Ephrin-B2 抑制对细胞增殖、凋亡、迁移、侵袭和管腔形成的影响。采用胎盘-蜕膜共培养（PDC）系统在体外验证 Ephrin-B2 诱导的滋养层细胞功能。在转录水平检测参与动脉重塑过程的因子，如基质金属蛋白酶（MMPs）、胎盘生长因子（PlGF）和血管内皮生长因子（VEGF）。
抑制 Ephrin-B2 可抑制 HTR-8/SVneo 细胞的增殖并诱导其凋亡。Ephrin-B2 的下调损害了 HTR-8/SVneo 细胞的迁移/侵袭能力，并显著降低了 MMPs 的基因表达。此外，Ephrin-B2 下调后观察到管腔形成较差且 PlGF 的基因表达降低。然而，VEGF-A 的基因表达未显示出显著的统计学差异。PDC 系统进一步证实了这些效应，显示滋养层细胞侵袭和螺旋动脉重塑不足。
Ephrin-B2 可能通过滋养层细胞侵袭和血管内形成在母体动脉重塑中起正调节作用。
