Department of Obstetrics, Xinhui People's Hospital of Southern Medical University, Jiangmen, 529100, Guangdong, China; Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, China; Department of Obstetrics, The People's Hospital of Rizhao, Rizhao, Shandong, 276800, China.
Department of Obstetrics, The People's Hospital of Rizhao, Rizhao, Shandong, 276800, China.
Eur J Pharmacol. 2023 Dec 5;960:176015. doi: 10.1016/j.ejphar.2023.176015. Epub 2023 Aug 29.
Preeclampsia (PE) harms a significant number of pregnant women and fetuses. However, because of its complex pathological mechanisms, there is no cure except for delivery. This study identified the impact and mechanisms of action of HOXB3 in PE. The behaviors of HTR-8/SVneo cells were analyzed using a cell counting kit-8, EdU, and transwell assays. The interaction between HOXB3 and Notch1 was assessed using a luciferase reporter and chromatin immunoprecipitation assays. Expression was measured by quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence assays. Additionally, the function of HOXB3 was evaluated in an established rat model of PE. We found that HOXB3 was upregulated in PE. HOXB3 overexpression facilitated trophoblast cell proliferation, migration, and invasion. HOXB3 transcriptionally regulated Notch1 by binding to its promoter. Notch1 knockdown abrogated the functions of HOXB3 and the-catenin pathway in trophoblasts. Suppression of the Wnt/β-catenin pathway abrogated the effects of HOXB3. Additionally, HOXB3 alleviated the symptoms in PE rats. In conclusion, HOXB3 transcriptionally activated Notch1 expression and the-catenin pathway, promoting trophoblast cell proliferation, invasion, and migration, thereby alleviating PE progression. This study provides a novel approach for PE therapy.
子痫前期（PE）会对大量孕妇和胎儿造成危害。然而，由于其复杂的病理机制，除了分娩之外，没有治愈方法。本研究旨在确定 HOXB3 在 PE 中的作用和作用机制。通过细胞计数试剂盒-8、EdU 和 Transwell 分析检测 HTR-8/SVneo 细胞的行为。通过荧光素酶报告和染色质免疫沉淀分析评估 HOXB3 与 Notch1 的相互作用。通过定量实时聚合酶链反应、western blot 和免疫荧光分析测量表达。此外，还在建立的 PE 大鼠模型中评估了 HOXB3 的功能。我们发现 HOXB3 在 PE 中上调。HOXB3 过表达促进滋养细胞增殖、迁移和侵袭。HOXB3 通过结合其启动子转录调控 Notch1。Notch1 敲低消除了 HOXB3 和-β-catenin 通路在滋养细胞中的作用。抑制 Wnt/β-catenin 通路消除了 HOXB3 的作用。此外，HOXB3 缓解了 PE 大鼠的症状。总之，HOXB3 转录激活 Notch1 表达和-β-catenin 通路，促进滋养细胞增殖、侵袭和迁移，从而缓解 PE 的进展。本研究为 PE 的治疗提供了一种新方法。
