Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Rd., Nanjing 210008, China.
Nanjing Medical University, Nanjing 210029, China.
Pregnancy Hypertens. 2020 Jul;21:14-22. doi: 10.1016/j.preghy.2020.04.007. Epub 2020 Apr 24.
Bradykinin B2 receptor (B2R) was decreased in early chorionic villi of pregnancies who progressed to severe preeclampsia (PE), suggesting downregulation of B2R may be involved in the pathogenesis of PE. The aim of this study was to investigate the possible roles of B2R in the pathophysiology of PE and its function in trophoblastic cells.
The expression of B2R in placentas from patients with early-onset severe PE (sPE) and LPS induced PE-like rats were detected. The roles of B2R in HTR-8/SVneo cells migration and invasion were analyzed through transfecting B2R overexpressing plasmid vector or B2R-specific siRNA. The effect of HTR-8/SVneo cells culture supernatant with high and low expressing B2R on human umbilical vein endothelial cells (HUVEC) capillary formation ability was also investigated.
We found that B2R expression was significantly decreased in placentas of patients with sPE and PE-like rats. In addition, siRNA-mediated down-regulation of B2R markedly inhibited the migration and invasion of HTR-8/SVneo cells. Conversely, over-expression of B2R significantly promoted the migration and invasion of HTR-8/SVneo cells. Furthermore, the culture supernatant from B2R-overexpressed-HTR-8/SVneo cells promoted the capillary formation of HUVEC through increasing placental growth factor (PlGF) levels, while the culture supernatant from si-B2R-HTR-8/SVneo cells had the opposite effects.
The decrease of B2R in placentas leads to the dysfunction of invasion, migration and angiogenesis of trophoblasts, which may be involved in the pathogenesis of PE.
在进展为严重先兆子痫（PE）的早期绒毛中，缓激肽 B2 受体（B2R）减少，表明 B2R 的下调可能参与了 PE 的发病机制。本研究旨在探讨 B2R 在 PE 病理生理学中的可能作用及其在滋养细胞中的功能。
检测了早发型重度 PE（sPE）患者和 LPS 诱导的 PE 样大鼠胎盘组织中 B2R 的表达。通过转染 B2R 过表达质粒载体或 B2R 特异性 siRNA，分析 B2R 在 HTR-8/SVneo 细胞迁移和侵袭中的作用。还研究了高表达和低表达 B2R 的 HTR-8/SVneo 细胞培养上清液对人脐静脉内皮细胞（HUVEC）毛细血管形成能力的影响。
我们发现 sPE 患者和 PE 样大鼠胎盘组织中 B2R 表达明显降低。此外，siRNA 介导的 B2R 下调显著抑制了 HTR-8/SVneo 细胞的迁移和侵袭。相反，B2R 的过表达显著促进了 HTR-8/SVneo 细胞的迁移和侵袭。此外，B2R 过表达-HTR-8/SVneo 细胞的培养上清液通过增加胎盘生长因子（PlGF）水平促进 HUVEC 的毛细血管形成，而 si-B2R-HTR-8/SVneo 细胞的培养上清液则有相反的作用。
胎盘组织中 B2R 的减少导致滋养细胞侵袭、迁移和血管生成功能障碍，这可能参与了 PE 的发病机制。
