中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (10): 1549-1552.doi: 10.4103/1673-5374.193223

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

TNF-β:具有促进轴突断端再生功能的细胞因子

  

  • 收稿日期:2016-10-28 出版日期:2016-10-31 发布日期:2016-10-31
  • 基金资助:
    该研究由奥克斯纳临床基金会支持

Transforming growth factor beta 1, a cytokine with regenerative functions

Wale Sulaiman1, *, Doan H. Nguyen2, *   

  1. 1 Ochsner Health System, Department of Neurosurgery, Back and Spine Center, Tulane University, New Orleans, LA, USA 2 Laboratory of Neural Injury and Regeneration, Ochsner Medical Center, New Orleans, LA, USA
  • Received:2016-10-28 Online:2016-10-31 Published:2016-10-31
  • Contact: Wale Sulaiman, M.D., Ph.D. or Doan H. Nguyen, Ph.D., wsulaiman@ochsner.org or doan.nguyen@ochsner.org.
  • Supported by:
    This work was supported by Ochsner Clinic Foundation.

摘要:

作者在过去几年的研究目标主要集中在如何促进神经损伤断端的轴突再生。具体来说,他们的重点是在调节SC恢复和轴突再生时转化生长因子β(TGF -β1 )的作用。TGF-β1是一种细胞因子,用于开发和组织稳态重要蛋白质的TGF-β超家族的成员。TGF-β的信号传导是通过称为Smad蛋白的家庭信号蛋白TGF-β的I型和II型丝氨酸/苏氨酸激酶受体和激活的结合介导。TGF-β主要参与神经损伤的修复。生长促进SC表型已经牵连TGF-β和若干神经营养因子的神经营养作用。临床实践中周围神经损伤修复延迟经常发生,也没有明确的临床指南能够确保显著的恢复。如果确实出现恢复,通常数月内都不是非常明显。此外,再生相关蛋白、轴突的再生和神经再支配肌肉的最大上调在4-6个星期内能够完全实现。超出这个时间窗,分子反应迅速,再生能力下降。以增加轴突生长和/或延长生长宽容的环境仍然是一个显著的挑战。

orcid: 0000-0002-0429-4101 (Doan H. Nguyen)

Abstract: "We review the biology and role of transforming growth factor beta 1 (TGF-β1) in peripheral nerve injury and regeneration, as it relates to injuries to large nerve trunks (i.e., sciatic nerve, brachial plexus), which ofen leads to suboptimal functional recovery. Experimental studies have suggested that the reason for the lack of functional recovery resides in the lack of sufcient mature axons reaching their targets, which is a result of the loss of the growth-supportive environment provided by the Schwann cells in the distal stump of injured nerves. Using an established chronic nerve injury and delayed repair animal model that accurately mimics chronic nerve injuries in humans, we summarize our key fndings as well as others to better understand the pathophysiology of poor functional recovery. We demonstrated that 6 month TGF-β1 treatment for chronic nerve injury signifcantly improved Schwann cell capacity to support axonal regeneration. When combined with forskolin, the e?ect was additive, as evidenced by a near doubling of regenerated axons proximal to the repair site. We showed that in vivo application of TGF-β1 and forskolin directly onto chronically injured nerves reactivated chronically denervated Schwann cells, induced their proliferation, and upregulated the expression of regeneration-associated proteins. Te e?ect of TGF-β1 and forskolin on old nerve injuries is quite impressive and the treatment regiment appears to mediate a growth-supportive milieu in the injured peripheral nerves. In summary, TGF-β1 and forskolin treatment reactivates chronically denervated Schwann cells and could potentially be used to extend and prolong the regenerative responses to promote axonal regeneration"

Key words: chronic nerve injuries, transforming growth factor, Schwann cells, axonal regeneration, regeneration-associated proteins, functional recovery