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转化生长因子-β1对大鼠坐骨神经损伤后的华勒氏变性至关重要。

TGF-β1 is critical for Wallerian degeneration after rat sciatic nerve injury.

作者信息

Li M, Zhang P, Li H, Zhu Y, Cui S, Yao D

机构信息

Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226019, PR China.

China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, PR China.

出版信息

Neuroscience. 2015 Jan 22;284:759-767. doi: 10.1016/j.neuroscience.2014.10.051. Epub 2014 Nov 4.

DOI:10.1016/j.neuroscience.2014.10.051
PMID:25451291
Abstract

Wallerian degeneration (WD) is a process of axonal degeneration distal to the injury site followed by a robust regenerative response. It involves degeneration and regeneration which can be directly induced by nerve injury and activated by transcription factors. Although WD has been studied extensively, the precise mechanisms of transcription factors regulating WD are still elusive. In this study, we reported the effect of transforming growth factor-β1 (TGF-β1) on WD after rat sciatic nerve injury. The data showed that TGF-β1 may express in injured rat sciatic nerve and cultured Schwann cells (SCs). Knock down of TGF-β1 expressions resulted in the reduction of SC proliferation and apoptosis, up regulation of cytokines and Smad2, 4. Enhanced expression of TGF-β1 could promote SC proliferation and apoptosis, down regulation of cytokines and Smad2, 4. Altered expressions of TGF-β1 may affect Smad and AKT but not c-Jun and extracellular regulated protein kinase (ERK) pathways. Our results revealed the role of TGF-β1 on WD and provided the basis for the molecular mechanisms of TGF-β1-regulated nerve degeneration and/or regeneration.

摘要

沃勒变性(WD)是损伤部位远端轴突变性的过程,随后是强烈的再生反应。它涉及变性和再生,可由神经损伤直接诱导并由转录因子激活。尽管对沃勒变性已进行了广泛研究,但转录因子调节沃勒变性的精确机制仍不清楚。在本研究中,我们报道了转化生长因子-β1(TGF-β1)对大鼠坐骨神经损伤后沃勒变性的影响。数据表明,TGF-β1可能在损伤的大鼠坐骨神经和培养的雪旺细胞(SCs)中表达。敲低TGF-β1表达导致雪旺细胞增殖和凋亡减少,细胞因子和Smad2、4上调。增强TGF-β1表达可促进雪旺细胞增殖和凋亡,细胞因子和Smad2、4下调。TGF-β1表达的改变可能影响Smad和AKT途径,但不影响c-Jun和细胞外调节蛋白激酶(ERK)途径。我们的结果揭示了TGF-β1在沃勒变性中的作用,并为TGF-β1调节神经变性和/或再生的分子机制提供了依据。

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