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首页> 外文期刊>Neuroscience: An International Journal under the Editorial Direction of IBRO >ACTIVATION OF THE WNT/beta-CATENIN SIGNALING CASCADE AFTER TRAUMATIC NERVE INJURY
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ACTIVATION OF THE WNT/beta-CATENIN SIGNALING CASCADE AFTER TRAUMATIC NERVE INJURY

机译：创伤性神经损伤后WNT /β-catenin信号级联的激活

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Recent data have shown that preservation of the neuromuscular junction (NMJ) after traumatic nerve injury helps to improve functional recovery with surgical repair via matrix metalloproteinase-3 (MMP3) blockade. As such, we sought to explore additional pathways that may augment this response. Wnt3a has been shown to inhibit acetylcholine receptor (AChR) clustering via beta-catenin-dependent signaling in the development of the NMJ. Therefore, we hypothesized that Wnt3a and beta-catenin are associated with NMJ destabilization following traumatic denervation. A critical size nerve defect was created by excising a 10-mm segment of the sciatic nerve in mice. Denervated muscles were then harvested at multiple time points for immunofluorescence staining, quantitative real-time PCR, and western blot analysis for Wnt3a and beta-catenin levels. Moreover, a novel Wnt/beta-catenin transgenic reporter mouse line was utilized to support our hypothesis of Wnt activation after traumatic nerve injury. The expression of Wnt3a mRNA was significantly increased by 2 weeks post-injury and remained upregulated for 2 months. Additionally, beta-catenin was activated at 2 months post-injury relative to controls. Correspondingly, immunohistochemical analysis of denervated transgenic mouse line TCF/Lef: H2B-GFP muscles demonstrated that the number of GFP-positive cells was increased at the motor endplate band. These collective data support that post-synaptic AChRs destabilize after denervation by a process that involves the Wnt/beta-catenin pathway. As such, this pathway serves as a potential therapeutic target to prevent the motor endplate degeneration that occurs following traumatic nerve injury. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
机译：最近的数据表明，创伤性神经损伤后神经肌肉接头（NMJ）的保存有助于通过基质金属蛋白酶3（MMP3）阻断进行手术修复，从而改善功能恢复。因此，我们试图探索可能增强这种反应的其他途径。已经显示，Wnt3a在NMJ的发育过程中会通过β-catenin依赖性信号传导抑制乙酰胆碱受体（AChR）聚集。因此，我们假设Wnt3a和β-连环蛋白与创伤性神经支配后的NMJ失稳有关。切除小鼠坐骨神经的10毫米部分会造成临界大小的神经缺损。然后在多个时间点采集神经支配的肌肉，以进行免疫荧光染色，实时定量PCR和Wnt3a和β-catenin水平的蛋白质印迹分析。此外，新型的Wnt /β-catenin转基因报告基因小鼠系被用于支持我们的创伤性神经损伤后Wnt激活的假说。损伤后2周，Wnt3a mRNA的表达显着增加，并持续上调2个月。另外，相对于对照，β-连环蛋白在损伤后2个月被激活。相应地，去神经化的转基因小鼠品系TCF / Lef：H2B-GFP肌肉的免疫组织化学分析表明，在运动终板带，GFP阳性细胞的数量增加了。这些集体数据支持突触后的AChR在去神经后通过涉及Wnt /β-catenin途径的过程失稳。这样，该途径可作为潜在的治疗靶标，以防止在创伤性神经损伤后发生的运动终板退化。 （C）2015年IBRO。由Elsevier Ltd.出版。保留所有权利。

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