AMD3100 inhibits the migration and differentiation of neural stem cells after spinal cord injury.
AMD3100 inhibits the migration and differentiation of neural stem cells after spinal cord injury.
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DOI：
10.1038/s41598-017-00141-8
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发表时间：
2017-03-06
影响因子：
4.6
通讯作者：
Liu ZL
中科院分区：
文献类型：
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作者：
Liu JM;Zhao K;Du LX;Zhou Y;Long XH;Chen XY;Liu ZL
据报道，CXCR4信号在脊髓损伤（SCI）后内源性神经干细胞的迁移和分化中发挥重要作用。然而，其分子机制仍不清楚。在这里，我们建立了大鼠 SCI 模型，并使用 AMD3100 对其进行治疗。然后处死大鼠并采集受伤的脊髓标本。此外，神经干细胞 (NSC) 系在体外培养并用 AMD3100 处理。结果显示，AMD3100治疗后SCI大鼠的运动功能更差。并且损伤脊髓中神经干细胞中的Nestion和神经元细胞中的β-微管蛋白的表达水平显着升高，并且可以被AMD3100的CXCR4拮抗剂抑制。此外，AMD3100 显着下调 β-catenin 和磷酸化酶 β-catenin 蛋白的表达。在体外，AMD3100处理后NSCs增殖能力受到抑制，迁移能力下降。此外，与未治疗组相比，AMD3100组中Nestion、β-tubulin、β-catenin和磷酸化酶β-catenin蛋白的表达显着降低。综上所述，本研究表明AMD3100可以抑制SCI大鼠内源性神经干细胞的迁移和分化。其机制可能是AMD3100通过靶向β-catenin信号通路下调SDF-1/CXCR4。
It was reported that CXCR4 signaling played an important role in the migration and differentiation of endogenous neural stem cells after spinal cord injury (SCI). However, the molecular mechanism of it is still unclear. Here, we established a model of SCI in rats and AMD3100 was used to treat them. The rats were then sacrificed and the injured spinal cord specimens were harvested. Additionally, the neural stem cells (NSCs) line was culture and treated with AMD3100 in vitro. Results showed the locomotor function of SCI rats was worse after treated with AMD3100. And the expression levels of Nestion in neural stem cells and β-tubulin in neuron cells were significantly increased in the injured spinal cord, which can be inhibited by the CXCR4 antagonist of AMD3100. Additionally, the expression of β-catenin and phosphorylase β-catenin protein was significantly down regulated by AMD3100. In vitro, the NSCs proliferation ability was inhibited and the migration was decreased after treated with AMD3100. Also, the expression of Nestion, β-tubulin, β-catenin and phosphorylase β-catenin protein was significantly decreased in AMD3100 group comparing with untreated group. Taken together, this study suggested that AMD3100 could inhibit the migration and differentiation of endogenous neural stem cells in rats with SCI. The mechanism of it maybe that AMD3100 could down regulate of SDF-1/CXCR4 by targeting β-catenin signaling pathway.