中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (2): 324-330.doi: 10.4103/1673-5374.226403

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

GSK3β抑制剂可用于解决周围神经损伤后的脱髓鞘和肌肉萎缩？

  

  • 收稿日期:2018-01-09 出版日期:2018-02-15 发布日期:2018-02-15
  • 基金资助:

    国家基础研究计划(973计划)资助（2014CB542201）；中国技术研究与发展计划(863计划)（SS2015AA020501）。国家自然科学基金（31571235，31771322，31671248，31571236，31271284，31171150，81171146，31471144，30971526，31100860，31040043，31371210和81372044）

GSK3β inhibitor promotes myelination and mitigates muscle atrophy after peripheral nerve injury

Jian Weng, Yan-hua Wang, Ming Li, Dian-ying Zhang, Bao-guo Jiang   

  1. Department of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, China
  • Received:2018-01-09 Online:2018-02-15 Published:2018-02-15
  • Contact: Dian-ying Zhang, Ph.D. or Bao-guo Jiang, Ph.D.,zdy8016@163.com or jiangbaoguo@vip.sina.com.
  • Supported by:

    This study was funded by the National Basic Research Program of China (973 Program), No. 2014CB542201; the National High Technology Research and Development Program of China (863 Program), No. SS2015AA020501; the National Natural Science Foundation of China (General Program), No. 31571235, 31771322, 31671248, 31571236, 31271284, 31171150, 81171146, 31471144, 30971526, 31100860,31040043, 31371210, and 81372044.

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摘要：

由于轴突再生的延迟，周围神经损伤通常会导致进行性肌肉萎缩和功能恢复不良。Wnt/β-catenin信号通路被认为是导致老年骨骼肌萎缩的主要分子机制之一。作者认为通过加速轴突再生和减慢肌肉细胞退化来促进靶肌肉的神经支配，可有利于改善周围神经损伤后骨骼肌的功能恢复，此过程可能与Wnt/β-catenin信号通路有关。因此，实验设计了体外细胞模型模拟髓鞘再生和肌肉萎缩的过程，分别观察了GSK3β抑制剂SB216763对许旺细胞系RSC96和肌细胞系C2C12的影响。发现SB216763刺激了许旺细胞迁移，并促进肌管收缩；qPCR检测显示，SB216763还可刺激髓鞘相关基因MAG和CCND1，肌肉相关基因MyoG和终板相关基因nAChRs的表达。免疫组织化学染色也显示，SB216763增加了RSC96和C2C12的细胞质及细胞核中β-catenin的免疫反应。这些数据说明，GSK 3β抑制剂通过Wnt/β-catenin信号通路促进许旺细胞髓鞘化和肌管分化，GSK3β抑制剂可能促进损伤周围神经再髓鞘化和减轻视神经支配肌肉萎缩的作用。

orcid:0000-0001-8436-5266(Bao-guo Jiang)

 

关键词: GSK 3&beta, 抑制剂, SB216763, 髓鞘化, 肌管分化, 失神经肌萎缩, Wnt/&beta, -catenin, 许旺细胞, 肌细胞, 神经再生, 周围神经损伤

Abstract:

Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mechanisms that lead to skeletal muscle atrophy in the elderly. We hold the hypothesis that the innervation of target muscle can be promoted by accelerating axon regeneration and decelerating muscle cell degeneration so as to improve functional recovery of skeletal muscle following peripheral nerve injury. This process may be associated with the Wnt/β-catenin signaling pathway. Our study designed in vitro cell models to simulate myelin regeneration and muscle atrophy. We investigated the effects of SB216763, a glycogen synthase kinase 3 beta inhibitor, on the two major murine cell lines RSC96 and C2C12 derived from Schwann cells and muscle satellite cells. The results showed that SB216763 stimulated the Schwann cell migration and myotube contraction. Quantitative polymerase chain reaction results demonstrated that myelin related genes, myelin associated glycoprotein and cyclin-D1, muscle related gene myogenin and endplate-associated gene nicotinic acetylcholine receptors levels were stimulated by SB216763. Immunocytochemical staining revealed that the expressions of β-catenin in the RSC96 and C2C12 cytosolic and nuclear compartments were increased in the SB216763-treated cells. These findings confirm that the glycogen synthase kinase 3 beta inhibitor,SB216763, promoted the myelination and myotube differentiation through the Wnt/β-catenin signaling pathway and contributed to nerve remyelination and reduced denervated muscle atrophy after peripheral nerve injury.

Key words: nerve regeneration, glycogen synthase kinase 3 beta inhibitor, SB216763, myelination, myotube differentiation, denervated muscle atrophy, Wnt/β-catenin, Schwann cell, muscle cells, peripheral nerve injury, neural regeneration