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 (24): 2151-2158.doi: 10.4103/1673-5374.147946

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

坐骨神经损伤后瓦勒变性早期紧密连接蛋白14的作用

  

  • 收稿日期:2014-11-22 出版日期:2014-12-25 发布日期:2014-12-25
  • 基金资助:

    国家自然科学基金（81370982; 31170946，81130080）

The effects of claudin 14 during early Wallerian degeneration after sciatic nerve injury

Leilei Gong 1, Yun Zhu 1, Xi Xu 1, Huaiqin Li 1, Weimin Guo 1, Qin Zhao 3, Dengbing Yao 1, 2   

  1. 1 Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong, Jiangsu Province, China
    2 School of Life Sciences, Nantong University, Nantong, Jiangsu Province, China
    3 Key Laboratory of People’s Liberation Army, Institute of Orthopedics, Chinese PLA General Hospital, Beijing, China
  • Received:2014-11-22 Online:2014-12-25 Published:2014-12-25
  • Contact: Dengbing Yao, M.D., Ph.D., Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong 226019, Jiangsu Province, China; School of Life Sciences, Nantong University, Nantong 226019, Jiangsu Province, China, yaodb@ntu.edu.cn.
  • Supported by:

    This research was supported by grants from the National Natural Science Foundation of China, Grant No. 81370982, 31170946, Key Program, Grant No. 81130080; the Scientific Research Foundation for Returned Scholars, Ministry of Education of China; the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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摘要：

课题组以往研究报道坐骨神经损伤大鼠Wallerian变性早期(0-4 d)，紧密连接蛋白14发生的促进损伤神经修复与再生的效应，但其机制仍不明确。本次研究揭示了紧密连接蛋白14在坐骨神经损伤大鼠瓦勒变性早期发挥作用的分子机制。表现为坐骨神经损伤瓦勒变性后(0-4 d)紧密连接蛋白14表达上调，调节许旺细胞中紧密连接蛋白14的表达可影响相应细胞因子的表达，对c-Jun信号通路具有显著影响，而对Akt和ERK1/2信号通路无影响。进一步验证显示，沉默许旺细胞中紧密连接蛋白14的表达可促进许旺细胞的凋亡，抑制细胞迁移；相反，增强其表达则可逆转上述变化。该研究从分子水平揭示了坐骨神经损伤瓦勒变性早期紧密连接蛋白14的作用机制。
 

关键词: 神经再生, 周围神经损伤, 瓦勒 变性, 坐骨神经损伤, 紧密连接蛋白14, 大鼠, 神经再生, 许旺细胞, 信号通路, c-jun, Akt, ERK1/2, 国家自然科学基金

Abstract:

Claudin 14 has been shown to promote nerve repair and regeneration in the early stages of Wallerian degeneration (0–4 days) in rats with sciatic nerve injury, but the mechanism underlying this process remains poorly understood. This study reported the effects of claudin 14 on nerve degeneration and regeneration during early Wallerian degeneration. Claudin 14 expression was up-regulated in sciatic nerve 4 days after Wallerian degeneration. The altered expression of claudin 14 in Schwann cells resulted in expression changes of cytokines in vitro. Expression of claudin 14 affected c-Jun, but not Akt and ERK1/2 pathways. Further studies revealed that enhanced expression of claudin 14 could promote Schwann cell proliferation and migration. Silencing of claudin 14 expression resulted in Schwann cell apoptosis and reduction in Schwann cell proliferation. Our data revealed the role of claudin 14 in early Wallerian degeneration, which may provide new insights into the molecular mechanisms of Wallerian degeneration.

Key words: nerve regeneration, peripheral nerve injury, Wallerian degeneration, sciatic nerve injury, Claudin 14, rat, Schwann cell, Signal pathways, c-Jun, Akt, ERK1/2, NSFC grant, neural regeneration