Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, China.
Institute of Developmental Biology, College of Life Science, Shandong University, Jinan, China.
Lab Invest. 2015 Dec;95(12):1439-49. doi: 10.1038/labinvest.2015.120. Epub 2015 Nov 2.
Granulocyte colony-stimulating factor (G-CSF) was investigated for its capacity to induce autophagy and related neuroprotective mechanisms in an acute spinal cord injury model. To accomplish this goal, we established a mouse spinal cord hemisection model to test the effects of recombinant human G-CSF. The results showed that autophagy was activated after spinal cord injury and G-CSF appears to induce a more rapid activation of autophagy within injured spinal cords as compared with that of non-treated animals. Apoptosis as induced in mechanically injured neurons with G-CSF treatment was enhanced after inhibiting autophagy by 3-methyladenine (3-MA), which partially blocked the neuroprotective effect of autophagy as induced by G-CSF. In addition, G-CSF inhibited the activity of the NF-κB signal pathway in neurons after mechanical injury. We conclude that G-CSF promotes autophagy by inhibiting the NF-κB signal pathway and protects neuronal structure after spinal cord injury. We therefore suggest that G-CSF, which rapidly induces autophagy after spinal cord injury to inhibit neuronal apoptosis, may thus provide an effective auxiliary therapeutic intervention for spinal cord injury.
粒细胞集落刺激因子（G-CSF）被研究用于在急性脊髓损伤模型中诱导自噬及其相关的神经保护机制。为了实现这一目标，我们建立了一个小鼠脊髓半切模型来测试重组人 G-CSF 的作用。结果表明，自噬在脊髓损伤后被激活，与未处理的动物相比，G-CSF 似乎在损伤的脊髓中诱导更快的自噬激活。用 3-甲基腺嘌呤（3-MA）抑制自噬后，G-CSF 处理的机械损伤神经元中的细胞凋亡增加，这部分阻断了 G-CSF 诱导的自噬的神经保护作用。此外，G-CSF 抑制了机械损伤后神经元中 NF-κB 信号通路的活性。我们得出结论，G-CSF 通过抑制 NF-κB 信号通路促进自噬，并保护脊髓损伤后的神经元结构。因此，我们建议 G-CSF 在脊髓损伤后迅速诱导自噬以抑制神经元凋亡，从而为脊髓损伤提供一种有效的辅助治疗干预措施。
