Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University , Nanjing , China.
Department of Obstetrics and Gynecology, Maternal and Child Healthcare Hospital of Shenzhen City, Southern Medical University , Shenzhen , China.
Am J Physiol Endocrinol Metab. 2019 May 1;316(5):E773-E781. doi: 10.1152/ajpendo.00383.2018. Epub 2019 Mar 12.
Preeclampsia (PE) is a major cause of maternal mortality and morbidity worldwide. Although there has been great progress in the understanding of PE, the exact cause for the disease development is still unclear. Recently, studies showed that genetic deletion of ELABELA (ELA, also known as APELA) could induce PE-like symptoms in mice. However, the role of ELA in the disease development of PE remains elusive. Our objective was to measure the changes of ELA levels in maternal serum, urine, and placenta from preeclamptic pregnant women and healthy pregnant women and evaluate the correlation between ELA levels and the occurrence of PE. Additionally, we investigated the effect of ELA on the migration and proliferation of human trophoblast cells. ELA levels are significantly decreased in late-onset PE pregnancies compared with normal pregnancies. The mRNA and protein expressions of ELA and the apelin receptor (APLNR or APJ) in late-onset PE placental tissues are also decreased. Furthermore, our in vitro study showed that the addition of ELA significantly increased the invasion ability and proliferation of trophoblast cells, which were inhibited by the APJ-specific antagonist ML221. Our study identified ELA as significantly decreased in late-onset PE; therefore, it might play an important role in the pathogenesis of late-onset PE.
子痫前期（PE）是全球孕产妇死亡和发病的主要原因。尽管人们对 PE 的认识已经取得了很大进展，但该病的确切发病原因仍不清楚。最近的研究表明，ELABELA（ELA，也称为 APELA）的基因缺失可在小鼠中诱导出类似 PE 的症状。然而，ELA 在 PE 疾病发展中的作用仍不清楚。我们的目的是测量子痫前期孕妇和健康孕妇的母血清、尿液和胎盘组织中 ELA 水平的变化，并评估 ELA 水平与 PE 发生之间的相关性。此外，我们还研究了 ELA 对人滋养层细胞迁移和增殖的影响。与正常妊娠相比，晚发型 PE 妊娠患者的 ELA 水平显著降低。晚发型 PE 胎盘组织中 ELA 和 apelin 受体（APLNR 或 APJ）的 mRNA 和蛋白表达也降低。此外，我们的体外研究表明，添加 ELA 可显著增加滋养层细胞的侵袭能力和增殖能力，而 APJ 特异性拮抗剂 ML221 可抑制这种作用。我们的研究表明，ELA 在晚发型 PE 中显著降低，因此，它可能在晚发型 PE 的发病机制中发挥重要作用。
