Potential role of FoxO3a in the regulation of trophoblast development and pregnancy complications.
Potential role of FoxO3a in the regulation of trophoblast development and pregnancy complications.
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FoxO3a 在调节滋养层发育和妊娠并发症中的潜在作用。
DOI：
10.1111/jcmm.16499
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发表时间：
2021-05
影响因子：
5.3
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Chen H;Tang X;Han TL;Zhu JN;Zhou W;Baker PN;Chen C;Zhang H
叉头盒O3 a蛋白（FoxO 3a）已被报道调节肿瘤的侵袭和迁移，但关于其在滋养层细胞侵袭和迁移到子宫中的分子机制或作用知之甚少。本研究旨在探讨其在滋养细胞发育和胎盘相关妊娠并发症中的作用及其可能机制。首先比较了健康孕妇和先兆子痫患者胎盘组织中FoxO 3a及其磷酸化形式（p-FoxO 3a）的水平。然后，用慢病毒载体转染HTR-8/SVneo细胞以耗尽和过表达FoxO 3a。对细胞进行Western印迹、免疫组织化学、Cell Counting Kit-8、伤口愈合测定、Matrigel侵袭测定、细胞凋亡、细胞周期测定、RNA测序、qRT-PCR和ChIP-qPCR，以研究FoxO 3a的潜在作用和潜在机制。我们发现FoxO 3a的表达减少，而p-FoxO 3a在先兆子痫胎盘中增加。在ChIP检测中，FoxO 3a缺失显著降低了细胞间粘附分子-1（ICAM 1）基因启动子区的转录，导致滋养层细胞侵袭和迁移减少，细胞周期停滞在G1期，并增加氧化应激下的凋亡。我们的研究结果表明，FoxO 3a可能在胎盘发育过程中的滋养层细胞的侵袭和迁移的调节中发挥作用，这可能是因为它与ICAM 1启动子的亲和力。
The forkhead box O3a protein (FoxO3a) has been reported to regulate tumour invasion and migration, but little is known about the molecular mechanism or its role in trophoblast invasion and migration into the uterus. In this study, we aim to explore its role in trophoblast development and placenta‐related pregnancy complications and the potential mechanism. Levels of FoxO3a and its phosphorylated form (p‐FoxO3a) in placental tissue from healthy pregnant women and pre‐eclampsia patients were first compared. Then, HTR‐8/SVneo cells were transfected with lentiviral vectors to deplete and overexpress FoxO3a. Western blot, immunohistochemistry, Cell Counting Kit‐8, wound‐healing assay, Matrigel invasion assay, cell apoptosis, cell cycle assay, RNA sequencing, qRT‐PCR and ChIP‐qPCR were performed on the cells to study the potential role of FoxO3a and the underlying mechanism. We found the expression of FoxO3a was decreased, whereas p‐FoxO3a was increased in pre‐eclampsia placentae. FoxO3a depletion significantly reduced transcription of the promoter region of intercellular cell adhesion molecule‐1 (ICAM1) gene in ChIP assays and led to reduced invasion and migration of trophoblast cells, arrested cell cycle in G1 phase and increased apoptosis under oxidative stress. Our results suggested that FoxO3a may play a role in the regulation of trophoblast invasion and migration during placental development, which may be because of its affinity to the ICAM1 promotor.
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