Imbalance between proliferation and apoptosis-related impaired GPR30 expression is involved in preeclampsia

Imbalance between proliferation and apoptosis-related impaired GPR30 expression is involved in preeclampsia
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增殖和凋亡之间的不平衡——相关的 GPR30 表达受损与先兆子痫有关

DOI:
10.1007/s00441-016-2466-y
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发表时间:
2016-11-01
影响因子:
3.6
通讯作者:
Zhang, Hua
Zhang, Hua
中科院分区:
生物学3区
文献类型:
--
作者:
Li, Jianxin;Chen, Zhu;Zhang, Hua

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胎盘细胞的增殖和凋亡在子痫前期中起重要作用,雌激素通过雌激素受体参与子痫前期的发病。一种新的ER,G蛋白偶联受体30(GPR30),最近被证明与PE有关。我们检测了正常胎盘和PE胎盘的增殖和凋亡的基本水平,并比较了两组胎盘GPR30的表达水平。我们证明低GPR30表达水平、更多的细胞凋亡和更少的增殖与PE相关。此外,我们的体外研究表明,选择性GPR30激动剂G1和一般ER激动剂17-β-雌二醇都能保护胎盘免受缺氧-复氧损伤,导致细胞凋亡减少,增殖增加。此外,选择性GPR30抑制剂G15的加入取消了这种保护作用。这些结果表明:(1)GPR30参与了细胞增殖和凋亡的调节;(2)GPR30的药理上调有利于PE的治疗;(3)GPR30可能是妊娠合并PE的干预靶点。
The proliferation and apoptosis of cells in the placenta play a critical role in preeclampsia (PE) in which estrogen has been implicated via estrogen receptors (ERs). A novel ER, G-protein-coupled receptor 30 (GPR30), has recently been shown to be involved in PE. We investigated the basic levels of proliferation and apoptosis in normal placentae and placentae with PE and compared GPR30 expression levels between the two groups. We demonstrated that low GPR30 expression levels, more apoptosis, and less proliferation were associated with PE. Moreover, our in vitro study showed that both the selective GPR30 agonist G1 and the general ER agonist 17-β-estradiol were able to protect the placenta from hypoxia-reoxygenation injuries, resulting in decreased apoptosis and increased proliferation. Furthermore, this protective effect was abolished by the addition of the selective GPR30 inhibitor G15. These results provide evidence that (1) GPR30 is involved in regulating cell proliferation and apoptosis; (2) pharmacologic upregulation of GPR30 is beneficial for PE management; (3) GPR30 may therefore be an interventional target for pregnancies complicated by PE.