Granulocyte colony-stimulating factor improves neuron survival in experimental spinal cord injury by regulating nucleophosmin-1 expression
Granulocyte colony-stimulating factor improves neuron survival in experimental spinal cord injury by regulating nucleophosmin-1 expression
复制标题
粒细胞集落刺激因子通过调节 nucleophosmin-1 表达改善实验性脊髓损伤中的神经元存活
DOI：
10.1002/jnr.23362
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发表时间：
2014-06-01
影响因子：
4.2
通讯作者：
Hao, Aijun
中科院分区：
文献类型：
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作者：
Guo, Yuji;Liu, Shangming;Hao, Aijun
本研究旨在探讨粒细胞集落刺激因子（G-CSF）对小鼠脊髓损伤的神经保护作用及其相关机制。将重组人粒细胞集落刺激因子（rhG-CSF）注射到脊髓半切模型小鼠体内。采用Basso-Bettie-Bresnahan量表评估自发活动。从脊髓分离的神经元在体外培养，并用于神经元机械损伤模型。将三个治疗组与该模型进行比较，1）G-CSF，2）G-CSF + NSC 348884（一种核磷蛋白1特异性抑制剂）和3）NSC 348884。免疫荧光染色和Western blotting检测G-CSF和核磷蛋白1（Npm 1）的表达。TUNEL染色分析G-CSF处理后细胞凋亡情况。我们发现G-CSF受体（G-CSFR）和Npm 1在神经元中表达，并且在G-CSF处理后诱导Npm 1表达。G-CSF抑制神经细胞凋亡。NSC 348884诱导p53依赖性细胞凋亡，并部分阻断G-CSF对体外神经元的神经保护作用。在急性脊髓损伤模型中，G-CSF促进运动恢复并表现出神经保护作用。G-CSF的神经保护机制可能部分与NPM 1减少神经元凋亡有关。(c)2014年威利期刊公司
Granulocyte colony-stimulating factor (G-CSF) and its related mechanisms were investigated to assess the potential for this factor to exert neuroprotective effects against spinal cord injury in mice. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was injected into mice spinal cord hemisection models. Locomotor activity was assessed by using the Basso-Bettie-Bresnahan scale. Neurons isolated from spinal cords were cultured in vitro and used in a neuronal mechanical injury model. Three treatment groups were compared with this model, 1) G-CSF, 2) G-CSF + NSC348884 (a nucleophosmin 1-specific inhibitor), and 3) NSC348884. Immunofluorescence staining and Western blotting were performed to analyze the expression of G-CSF and nucleophosmin 1 (Npm1). TUNEL staining was performed to analyze apoptosis after G-CSF treatment. We found that the G-CSF receptor (G-CSFR) and Npm1 were expressed in neurons and that Npm1 expression was induced after G-CSF treatment. G-CSF inhibited neuronal apoptosis. NSC348884 induced p53-dependent cell apoptosis and partially blocked the neuroprotective activity of G-CSF on neurons in vitro. G-CSF promoted locomotor recovery and demonstrated neuroprotective effects in an acute spinal cord injury model. The mechanism of G-CSF's neuroprotection may be related in part to attenuating neuronal apoptosis by NPM1. (c) 2014 Wiley Periodicals, Inc.