中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (18): 1688-1695.doi: 10.4103/1673-5374.141804

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

骨髓间充质干细胞为何向损伤脊髓定向迁移？

  

  • 收稿日期:2014-06-13 出版日期:2014-09-26 发布日期:2014-09-26
  • 基金资助:

    国家自然科学基金资助项目（81350013，81250016）；国家自然科学基金青年科学基金项目（81301289）；吉林省科技发展计划青年科研基金项目（20130522032JH，20130522039JH）

Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord

Peng Xia 1, Su Pan 1, Jieping Cheng 1, Maoguang Yang 2, Zhiping Qi 1, Tingting Hou 1, Xiaoyu Yang 1   

  1. 1 Department of Spine Surgery, Orthopedics Hospital, Second Hosptal, Jilin University, Changchun, Jilin Province, China
    2 Department of Endocrinology, Second Hosptal, Jilin University, Changchun, Jilin Province, China
  • Received:2014-06-13 Online:2014-09-26 Published:2014-09-26
  • Contact: Xiaoyu Yang, Department of Spine Surgery, Orthopedics Hospital, Second Hosptal, Jilin University, Changchun 130041, Jilin Province, China,yangxiaoyu88@sina.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81350013, 81250016; the Youth Science Project of National Natural Science Foundation of China, No. 81301289; the Youth Scientific Research Project of Jilin Provincial Science and Technology Development Plan, No. 20130522032JH, 20130522039JH.

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摘要：

已有研究证实在轴突导向与神经元迁移过程中微管相关蛋白1B发挥重要作用。为此，作者设了此实验希望揭示其机制。首先发现蛋白磷酸酶2A活性抑制剂冈田酸和蛋白磷酸酶2A活性激动剂乙酰化-D-赤式-二氢神经鞘氨醇干预骨髓间充质干细胞24h，均能影响细胞中蛋白磷酸酶2A活性，且细胞中I型微管相关蛋白1B 磷酸化形式的表达水平分别出现增多和减少；将经冈田酸和乙酰化-D-赤式-二氢神经鞘氨醇干预骨髓间充质干细胞经耳缘静脉注射移植治疗脊髓挫伤模型兔后，见细胞迁移效果明显不如未经处理的骨髓间充质干细胞；而分别利用磷酸化抑制剂LY294002与U0126阻断兔骨髓间充质干细胞内磷脂酰肌醇3-激酶和ERK1/2通路后，细胞中I型微管相关蛋白1B磷酸化形式分别升高和降低。说明骨髓间充质干细胞内磷脂酰肌醇3-激酶与ERK1/2会通过交叉信号网络影响微管相关蛋白1B的磷酸化，从而影响骨髓间充质干细胞向损伤脊髓迁移的效率。

关键词: 神经再生, 骨髓间充质干细胞, 脊髓损伤, 微管相关蛋白1B, 蛋白磷酸酶2A, 细胞移植, 磷酸化作用, 信号转导, NSFC grant

Abstract:

Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtubule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of microtubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord.

Key words: nerve regeneration, bone marrow mesenchymal stem cells, spinal cord injury, microtubule- associated protein 1B, protein phosphatase 2A, cell transplantation, phosphorylation, signal transduction, NSFC grant, neural regeneration