Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, China.
Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, China.
Placenta. 2023 Sep 7;140:20-29. doi: 10.1016/j.placenta.2023.07.010. Epub 2023 Jul 20.
To investigate the role of claudin-1 (CLDN1) in trophoblast invasion and endovascular trophoblast (enEVT) differentiation in early-onset preeclampsia (EOPE).
The expression and localization of CLDN1 in normal (n = 18) and EOPE (n = 20) placental tissues were detected by immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction (qRT‒PCR) and Western blotting. Next, invasion, migration and tube formation assays were performed to explore the involvement of CLDN1 in trophoblast invasion and enEVT differentiation in trophoblast cell lines (HTR8/SVneo). Then, invasion and enEVT markers were analyzed via Western blotting and qRT‒PCR, respectively. Finally, we established an EOPE mouse model to detect the Cldn1 protein level.
CLDN1 expression was significantly decreased in EOPE placental tissues. Knockdown of CLDN1 suppressed HTR8/SVneo cell invasion, migration and the ability to penetrate the endothelial tube. Conversely, overexpression of CLDN1 promoted trophoblast invasion and the ability to invade the endothelial tube. Inhibition of CLDN1 decreased the protein expression of VIM and SNAIL along with downregulating IL1B and PECAM1 mRNA levels, while overexpression of CLDN1 gave the opposite results. In the EOPE mouse model, we found a decrease in Cldn1 expression in EOPE mouse placentas.
These results suggest that the downregulation of CLDN1 in trophoblast cells is involved in the pathogenesis of early-onset preeclampsia by affecting trophoblast invasion and enEVT differentiation.
本研究旨在探讨紧密连接蛋白 1（CLDN1）在早发型子痫前期（EOPE）中滋养细胞侵袭和血管内滋养细胞（enEVT）分化中的作用。
通过免疫组织化学（IHC）染色、实时定量聚合酶链反应（qRT-PCR）和 Western blot 检测正常（n=18）和 EOPE（n=20）胎盘组织中 CLDN1 的表达和定位。接下来，通过侵袭、迁移和管形成实验研究 CLDN1 在滋养细胞系（HTR8/SVneo）中对滋养细胞侵袭和 enEVT 分化的影响。然后，通过 Western blot 和 qRT-PCR 分别分析侵袭和 enEVT 标志物。最后，建立 EOPE 小鼠模型检测 Cldn1 蛋白水平。
EOPE 胎盘组织中 CLDN1 表达明显下调。CLDN1 敲低抑制 HTR8/SVneo 细胞侵袭、迁移和穿透内皮管的能力。相反，CLDN1 的过表达促进滋养细胞侵袭和穿透内皮管的能力。CLDN1 抑制降低了 VIM 和 SNAIL 的蛋白表达，并下调了 IL1B 和 PECAM1 mRNA 水平，而过表达 CLDN1 则产生相反的结果。在 EOPE 小鼠模型中，我们发现 EOPE 小鼠胎盘中 Cldn1 表达减少。
这些结果表明，CLDN1 在滋养细胞中的下调通过影响滋养细胞侵袭和 enEVT 分化参与了早发型子痫前期的发病机制。
