Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou.
Department of Orthodontics, Stomatological Clinic, Zhongshan People's Hospital of Sun Yat-sen University, Zhongshan.
Eur J Histochem. 2021 Nov 25;65(4):3323. doi: 10.4081/ejh.2021.3323.
Preeclampsia (PE) is one of the leading causes of maternal morbidity and mortality in pregnant women. This study aimed to investigate the potential impact and regulatory mechanisms of bone morphogenetic protein receptor 2 (BMPR2) on the progression of PE. We obtained placental tissues from pregnant women with PE and normal pregnant women, and the results showed that BMPR2 was expressed at low levels in the tissue from PE women. Genetic knockdown of BMPR2 increased the proliferation and invasion of cultured trophoblast cells, whereas its overexpression reduced these characteristics. Bioinformatics analysis and luciferase reporter gene assays confirmed that BMPR2 is a direct target of miR-21. Overexpression of a miR-21 inhibitor promoted the growth and invasiveness of trophoblast cells, whereas the opposite results were observed for the miR-21 mimic. Furthermore, miR-21 was sponged by the lncRNA MEG3, and shRNA inhibition of MEG3 reduced trophoblast cell growth and invasiveness. miR-21 was upregulated in the tissues from PE women, whereas MEG3 was downregulated, and the two were negatively correlated. Collectively, this study demonstrates that the lncRNA MEG3 acts as a sponge for miR-21, which regulates BMPR2 expression and promotes trophoblast cell proliferation and invasiveness, thereby preventing the development of PE. These findings provide novel insight into a targeted therapy that could be used to treat or prevent the development of PE.
子痫前期（PE）是导致孕妇发病率和死亡率的主要原因之一。本研究旨在探讨骨形态发生蛋白受体 2（BMPR2）对 PE 进展的潜在影响和调节机制。我们从患有 PE 和正常妊娠的孕妇中获得胎盘组织，结果表明 BMPR2 在 PE 妇女的组织中表达水平较低。BMPR2 的基因敲低增加了培养的滋养层细胞的增殖和侵袭能力，而其过表达则降低了这些特征。生物信息学分析和荧光素酶报告基因检测证实 BMPR2 是 miR-21 的直接靶标。miR-21 抑制剂的过表达促进了滋养层细胞的生长和侵袭能力，而 miR-21 模拟物则观察到相反的结果。此外，miR-21 被 lncRNA MEG3 海绵吸附，shRNA 抑制 MEG3 减少滋养层细胞的生长和侵袭。PE 妇女组织中的 miR-21 上调，而 MEG3 下调，两者呈负相关。综上所述，本研究表明 lncRNA MEG3 作为 miR-21 的海绵，调节 BMPR2 的表达，促进滋养层细胞的增殖和侵袭，从而防止 PE 的发展。这些发现为靶向治疗提供了新的见解，可用于治疗或预防 PE 的发展。
