Formyl peptide receptors promotes neural differentiation in mouse neural stem cells by ROS generation and regulation of PI3K-AKT signaling.
Formyl peptide receptors promotes neural differentiation in mouse neural stem cells by ROS generation and regulation of PI3K-AKT signaling.
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甲酰基肽受体通过ROS的产生和PI3KAKT信号传导的调节促进小鼠神经干细胞的神经分化
DOI：
10.1038/s41598-017-00314-5
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发表时间：
2017-03-16
影响因子：
4.6
通讯作者：
Zhao J
中科院分区：
文献类型：
--
作者：
Zhang L;Wang G;Chen X;Xue X;Guo Q;Liu M;Zhao J
本研究旨在探讨甲酰肽受体（FPRs）是否参与神经干细胞（NSCs）的分化。FPRs在体外和体内均促进NSC的迁移。然而，FPRs在神经干细胞分化过程中的作用尚不清楚。Western blot分析显示，FPR 1和FPR 2在神经干细胞分化过程中表达明显增加。FPRs的激活促进NSCs分化为具有更多初级神经突和分支点以及每个细胞更长神经突的神经元。同时，这种激活也抑制了NSC向星形胶质细胞的分化。这种双向作用可被FPRs特异性抑制剂抑制。此外，发现FPRs的激活增加了NSC中活性氧（ROS）的产生和AKT的磷酸化，而N-乙酰半胱氨酸和LY 294002抑制了FPRs刺激的ROS产生和AKT磷酸化的增加，并阻断了FPRs刺激的神经分化为神经元。因此，FPRs刺激的神经分化是通过ROS和PI 3 K-AKT信号通路介导的。总的来说，目前的研究结果提供了一个新的洞察FPRs在神经发生中的功能作用，其潜在用途作为治疗脑或脊髓损伤的候选人具有重要意义。
This study aimed to determine whether formyl peptide receptors (FPRs) regulated the differentiation of neural stem cells (NSCs). FPRs promote the migration of NSCs both in vitro and in vivo. However, the role of FPRs during differentiation of NSCs is unknown. Analysis by Western blot showed significantly increased expression of FPR1 and FPR2 during differentiation of NSCs. The activation of FPRs promotes NSCs to differentiate into neurons with more primary neurites and branch points and longer neurites per cell. Meanwhile, this activation also inhibits the differentiation of NSC into astrocytes. This bidirectional effect can be inhibited by the FPRs-specific inhibitor. Moreover, it was found that the activation of FPRs increased the generation of reactive oxygen species (ROS) and phosphorylation of AKT in the NSCs, while N-acetylcysteine and LY294002 inhibited the FPRs-stimulated increase in ROS generation and AKT phosphorylation, and blocked the FPRs-stimulated neural differentiation into neurons. Therefore, FPRs-stimulated neural differentiation was mediated via ROS and PI3K-AKT signaling pathways. Collectively, the present findings provided a novel insight into the functional role of FPRs in neurogenesis, with important implications for its potential use as a candidate for treating brain or spinal cord injury.