中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (8): 1833-1840.doi: 10.4103/1673-5374.332159

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

周围神经来源成纤维细胞分泌神经营养因子促进运动神经元的轴突生长

  

  • 出版日期:2022-08-15 发布日期:2022-01-22
  • 基金资助:
    国家重点研发计划项目(2017YFA0104703);国家自然科学基金项目(重大项目)(92068112);南通科技计划项目(JC2020035);国家自然科学基金项目(31500927,31870977);江苏高等学校优先学术计划发展项目

Peripheral nerve fibroblasts secrete neurotrophic factors to promote axon growth of motoneurons

Qian-Ru He#, Meng Cong#, Fan-Hui Yu, Yu-Hua Ji, Shu Yu, Hai-Yan Shi, Fei Ding*   

  1. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, Jiangsu Province, China
  • Online:2022-08-15 Published:2022-01-22
  • Contact: Fei Ding, MS, dingfei@ntu.edu.cn.
  • Supported by:
    This study was supported by the National Key Research and Development Program of China, No. 2017YFA0104703 (to FD); the National Natural Science Foundation of China (Major Program), No. 92068112 (to FD); Science and Technology Program of Nantong of China, No. JC2020035 (to QRH); National Natural Science Foundation of China, Nos. 31500927 (to QRH) and 31870977 (to HYS) and the Priority Academic Program Development of Jiangsu High Education Institutions (PAPD) (to FD).

摘要:

周围神经成纤维细胞在神经发育和再生过程中起关键作用。作者既往研究已发现周围神经成纤维细胞存在着不同的感觉与运动表型,而不同表型的成纤维细胞可引导与之相同感觉或运动表型许旺细胞迁移。此次实验分析了周围神经来源成纤维细胞和心脏来源成纤维细胞对运动神经元产生的不同影响。与心脏来源成纤维细胞相比,神经来源成纤维细胞可显著促进体外运动神经元轴突的生长。高通量测序结果显示神经来源成纤维细胞和心脏来源成纤维细胞间总共491种差异表达的基因,其中神经来源成纤维细胞中有130种基因比心脏来源成纤维细胞上调,而这些基因可能参与轴突引导和神经元投射。大鼠坐骨神经横断3d后,其近端和远端残端都聚集大量神经来源成纤维细胞,其中大部分可表达脑源性神经营养因子。而在体外,从神经来源成纤维细胞分泌的脑源性神经营养因子可通过ERK和AKT信号通路增加β-肌动蛋白和F-肌动蛋白的表达,并增强运动神经元的轴突生长。提示不同来源的成纤维细胞存在不同的基因表达模式,而神经来源成纤维细胞可显著促进运动神经元轴突的生长。

https://orcid.org/0000-0002-7924-7545 (Qian-Ru He); https://orcid.org/0000-0002-9517-2707 (Fei Ding)

关键词: 成纤维细胞, 运动神经元, 轴突生长, 脑源性神经营养因子, 周围神经系统, mRNA测序, 差异基因表达, β-actin, F-actin

Abstract: Peripheral nerve fibroblasts play a critical role in nerve development and regeneration. Our previous study found that peripheral nerve fibroblasts have different sensory and motor phenotypes. Fibroblasts of different phenotypes can guide the migration of Schwann cells to the same sensory or motor phenotype. In this study, we analyzed the different effects of peripheral nerve-derived fibroblasts and cardiac fibroblasts on motoneurons. Compared with cardiac fibroblasts, peripheral nerve fibroblasts greatly promoted motoneuron neurite outgrowth. Transcriptome analysis results identified 491 genes that were differentially expressed in peripheral nerve fibroblasts and cardiac fibroblasts. Among these, 130 were significantly upregulated in peripheral nerve fibroblasts compared with cardiac fibroblasts. These genes may be involved in axon guidance and neuron projection. Three days after sciatic nerve transection in rats, peripheral nerve fibroblasts accumulated in the proximal and distal nerve stumps, and most expressed brain-derived neurotrophic factor. In vitro, brain-derived neurotrophic factor secreted from peripheral nerve fibroblasts increased the expression of β-actin and F-actin through the extracellular regulated protein kinase and serine/threonine kinase pathways, and enhanced motoneuron neurite outgrowth. These findings suggest that peripheral nerve fibroblasts and cardiac fibroblasts exhibit different patterns of gene expression. Peripheral nerve fibroblasts can promote motoneuron neurite outgrowth.

Key words: brain-derived neurotrophic factor, differential gene expression, F-actin, fibroblasts, motoneurons, mRNA sequencing, neurite outgrowth, peripheral nervous system, β-actin