国际妇产科学杂志

国际妇产科学杂志 ›› 2019, Vol. 46 ›› Issue (5): 490-493.

• 综述 • 上一篇    下一篇

P27基因参与子痫前期发生机制的研究进展

范卓然，顾艳，华绍芳   

  1. 300070 天津医科大学（范卓然）；天津医科大学第二医院计划生育科（顾艳），产科（华绍芳）
  • 收稿日期:2019-02-03 修回日期:2019-02-28 出版日期:2019-10-15 发布日期:2019-10-21
  • 通讯作者: 华绍芳，E-mail：hsf1974@126.com E-mail:hsf1974@126.com
  • 基金资助:
    国家自然科学基金（81701445）

The Research Progress in the Mechanism of P27 Gene in Pre-Eclampsia Pathogenesis

FAN Zhuo-ran, GU Yan, HUA Shao-fang   

  1. Tianjin Medical University, Tianjin 300070, China (FAN Zhuo-ran); Department of Family Planning (GU Yan), Department of Obstetrics (HUA Shao-fang), The Second Hospital of Tianjin Medical University, Tianjin 300211, China
  • Received:2019-02-03 Revised:2019-02-28 Published:2019-10-15 Online:2019-10-21
  • Contact: HUA Shao-fang, E-mail: hsf1974@126.com E-mail:hsf1974@126.com
  • Supported by:
     

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摘要： 子痫前期（pre-eclampsia，PE）是妊娠期特发疾病，其发生与发展是导致母儿患病率、死亡率增加的重要原因，胎盘中滋养细胞正常的增殖、迁移与分化与其关系密切。P27作为细胞周期蛋白依赖性激酶抑制剂（cyclin dependent kinase inhibitors，CKIs），与细胞周期因子结合调控细胞周期。与正常孕妇相比，PE患者胎盘滋养细胞中P27基因的表达明显增加，这可能与滋养细胞的增殖及侵入障碍有关。P27蛋白与不同蛋白质结合发挥不同作用，其调节主要依靠翻译后修饰及亚细胞定位。Nodal作为转化生长因子β（transforming growth factor β，TGF-β）的成员，在滋养细胞中通过多种机制上调P27 mRNA和蛋白水平，提高了P27蛋白的稳定性并在S10处诱导了P27蛋白的磷酸化，促使P27蛋白和CDK2向细胞质的转移，且加强P27/CDK2/CDK5/Stathmin的结合，从而抑制了细胞增殖、迁移及侵袭。P27蛋白在许多位点被磷酸化，氧化应激、蛋白激酶B（protein kinase B，Akt）、蛋白O-岩藻糖基转移酶1（protein O-fucosyltransferase 1，poFUT1）、磷酸果糖-2-激酶/果糖-2，6-二磷酸酶（PFKFB1-4）等通过使P27蛋白磷酸化，影响其泛素-蛋白酶体降解途径调节细胞周期进程。

关键词: 先兆子痫, 胎盘, P27蛋白, 细胞周期, 细胞增殖

Abstract: Pre-eclampsia (PE) is a disease special to pregnancy. Its occurrence and development is an important reason for the increase of maternal and infant morbidity and mortality. Normal proliferation, migration and differentiation of trophoblasts in placenta are closely related to it. P27 acts as a cyclin dependent kinase inhibitors (CKIs), which regulates cell cycle by binding to cell cycle factors. Compared with normal pregnant women, the expression of P27 gene in placental trophoblasts of PE patients increased significantly, which may be related to the dysfunction of trophoblast proliferation and invasion. Nodal, as a member of transforming growth factor β (TGF-β), up-regulates the level of P27 mRNA and protein in trophoblast cells through various mechanisms, improves the stability of P27 protein and induces phosphorylation of P27 protein at S10, promotes the transfer of P27 protein and CDK2 to cytoplasm, and enhances the binding of P27/CDK2/CDK5/Stathmin, thus inhibiting cell proliferation and migration，transfer and invasion. P27 protein is phosphorylated at many siｔｅｓ, oxidative stress, protein kinase B (Akt), protein O-fucosyltransferase 1 (poFUT1), fructose-2-kinase/fructose-2, 6-diphosphatase (PFKFB1-4) affect the ubiquitin-proteasome degradation pathway by phosphorylating P27 protein.

Key words: Pre-eclampsia, Placenta, P27 protein, Cell cycle, Cell proliferation

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