Neuroprotection of netrin-1 on neurological recovery via Wnt/β-catenin signaling pathway after spinal cord injury
Neuroprotection of netrin-1 on neurological recovery via Wnt/β-catenin signaling pathway after spinal cord injury
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脊髓损伤后 netrin-1 通过 Wnt/β-catenin 信号通路对神经恢复的神经保护作用
DOI：
10.1097/wnr.0000000000001441
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发表时间：
2020-04
期刊：
影响因子：
1.7
通讯作者：
Xiaoqian Dang
中科院分区：
文献类型：
--
作者：
Kai Gao;Jianbing Niu;Xiaoqian Dang
netrin-1在脊髓损伤后的神经保护作用及其具体的分子机制尚未阐明。在我们的研究中，Western blot、转移酶UTP缺口端标记染色和免疫荧光染色首先显示netrin-1显著降低脊髓损伤后caspase-3、caspase-9、转移酶UTP缺口端标记阳性神经元、核因子kappa-B、肿瘤坏死因子-α的表达水平，抑制神经元凋亡和炎症反应。通过Nissl和HE染色，我们还发现netrin-1显著增加脊髓前角的Nissl小体数量，促进脊髓损伤后损伤组织的恢复，从而为运动功能的恢复提供了良好的微环境。最后，Basso, Beattie， Bresnahan评分结果进一步证实netrin-1促进脊髓损伤后神经功能的恢复。netrin-1显著促进β-catenin的表达，抑制糖原合成酶激酶3β的表达，激活脊髓损伤后Wnt/β-catenin信号通路。而XAV939抑制Wnt/β-catenin信号通路，显著抑制netrin-1对细胞凋亡、炎症、Nissl小体、损伤组织和神经保护的调节作用。这些结果首次证实了netrin-1与脊髓损伤后Wnt/β-catenin信号通路的相关性，表明netrin-1通过激活脊髓损伤后Wnt/β-catenin信号通路发挥神经保护作用。
The neuroprotective effects of netrin-1 after spinal cord injury and its specific molecular mechanisms have not been elucidated. In our study, Western blot, transferase UTP nick end labeling staining and immunofluorescence staining first showed that netrin-1 significantly decreased the expression levels of caspase-3, caspase-9, transferase UTP nick end labeling-positive neurons, nuclear factor kappa-B, and tumor necrosis factor-α after spinal cord injury, which inhibited neuronal apoptosis and inflammatory response. Using Nissl and HE staining, we also found that netrin-1 significantly increased the number of Nissl bodies in the anterior horn of spinal cord and promoted the recovery of injured tissue after spinal cord injury, consequently providing a good microenvironment for recovery of motor function. Finally, the results of Basso, Beattie, and Bresnahan score further confirmed that netrin-1 promoted the recovery of neurological function after spinal cord injury. Furthermore, netrin-1 significantly promoted the expression of β-catenin and inhibited the expression of glycogen synthase kinase-3β, which activated Wnt/β-catenin signaling pathway after spinal cord injury. However, XAV939 inhibited Wnt/β-catenin signaling pathway, which significantly inhibited the regulatory effect of netrin-1 on apoptosis, inflammation, Nissl bodies, damaged tissues, and neuroprotection. These results demonstrate for the first time the correlation between netrin-1 and Wnt/β-catenin signaling pathway after spinal cord injury and show that netrin-1 exerts its neuroprotective effect by activating this signaling pathway after spinal cord injury.
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影响因子：
5.3
作者：
Bai L;Mei X;Wang Y;Yuan Y;Bi Y;Li G;Wang H;Yan P;Lv G
通讯作者：
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影响因子：
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影响因子：
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DOI：
10.1016/j.bbrc.2016.07.006
发表时间：
2016-09
影响因子：
3.1
作者：
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通讯作者：
Nicholas S. Strand;K. K. Hoi-K.;T. Phan;Catherine A. Ray;J. Berndt;R. Moon
影响因子：
5.1
作者：
Lambert, Catherine;Cisternas, Pedro;Inestrosa, Nibaldo C.
通讯作者：
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