中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (6): 983-987.doi: 10.4103/1673-5374.184499

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

体外实验发现抑制YAP表达上调可促进中枢神经干细胞突起生长

  

  • 收稿日期:2016-04-28 出版日期:2016-06-30 发布日期:2016-06-30
  • 基金资助:

    中国国家自然科学基金项目(30872602)

ROCK inhibition enhances neurite outgrowth in neural stem cells by upregulating YAP expression in vitro

Xu-feng Jia1, #, Fei Ye2, #, Yan-bo Wang2, Da-xiong Feng2, *   

  1. 1 Department of Orthopedic Surgery, Jianyang People’s Hospital of Sichuan Province, Jianyang, Sichuan Province, China 2 Department of Spine Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China
  • Received:2016-04-28 Online:2016-06-30 Published:2016-06-30
  • Contact: Da-xiong Feng, M.D., fdxlz2002@163.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China (General Program), No. 30872602.

摘要:

有研究显示脊髓损伤后,由于存在髓磷脂及其他抑制因子,导致神经元不能出现自发的轴突再生,而阻断Rho/ROCK通路可促进脊髓损伤模型中神经突起的生长。为此,课题组设计了抑制ROCK对小鼠脑室下区神经干细胞突起生长的实验方案。体外实验结果发现,以特异性ROCK抑制剂Y-27632干预神经干细胞后,神经干细胞突起长度增加,神经干细胞中Hippo信号通路的主要下游效应子YAP表达上调。表明抑制ROCK,可通过激活Hippo信号通路的途径介导神经干细胞的突起生长。

orcid: 0000-0002-2457-8187 (Xu-feng Jia)

关键词: 神经再生, 脊髓损伤, 神经干细胞, Rho信号通路, 神经突起, 髓磷脂, YAP

Abstract:

Spontaneous axonal regeneration of neurons does not occur after spinal cord injury because of inhibition by myelin and other inhibitory factors. Studies have demonstrated that blocking the Rho/Rho-kinase (ROCK) pathway can promote neurite outgrowth in spinal cord injury models. In the present study, we investigated neurite outgrowth and neuronal differentiation in neural stem cells from the mouse subventricular zone after inhibition of ROCK in vitro. Inhibition of ROCK with Y-27632 increased neurite length, enhanced neuronal differentiation, and upregulated the expression of two major signaling pathway effectors, phospho-Akt and phospho-mitogen-activated protein kinase, and the Hippo pathway effector YAP. These results suggest that inhibition of ROCK mediates neurite outgrowth in neural stem cells by activating the Hippo signaling pathway.

Key words: nerve regeneration, spinal cord injury, neural stem cells, Rho signaling pathway, neurite outgrowth, myelin, YAP, neural regeneration