中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (7): 1308-1316.doi: 10.4103/1673-5374.301024

• 原著:退行性病与再生 • 上一篇    下一篇

转铁蛋白受体1可在肌肉发育以及失神经支配引起肌萎缩中发挥重要作用

  

  • 出版日期:2021-07-15 发布日期:2021-01-07
  • 基金资助:

    国家自然科学基金面上项目(31770929,31520029,81902847);北京市科委项目(Z181100001518001,Z161100000216154)

Transferrin receptor 1 plays an important role in muscle development and denervation-induced muscular atrophy

Ying Li1, #, Juan-Xian Cheng1, #, Hai-Hong Yang1, 2, Li-Ping Chen1, Feng-Jiao Liu1, Yan Wu1, Ming Fan1, 3, Hai-Tao Wu1, 3, 4, *   

  1. 1 Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, China;  2 Department of Anesthesiology, the General Hospital of Western Theater Command, Chengdu, Sichuan Province, China;  3 Chinese Institute for Brain Research (CIBR), Beijing, China;  4 Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China 
  • Online:2021-07-15 Published:2021-01-07
  • Contact: Hai-Tao Wu, PhD, wuht@bmi.ac.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 31770929 (to HTW), 31522029 (to HTW), 81902847 (to HHY), and the Beijing Municipal Science and Technology Commission of China, Nos. Z181100001518001 (to HTW), Z161100000216154 (to HTW).

摘要:

既往研究表明转铁蛋白受体1及其配体转铁蛋白在再生的周围神经中积累,但是它们在失神经支配骨骼肌中的表达和功能仍不完全清楚。实验首先通过左侧臂丛神经完全撕裂建立小鼠失神经支配模型,RNA深度测序发现在失神经的骨骼肌中转铁蛋白表达上调,而转铁蛋白受体1下调。而后在条件性和诱导性转铁蛋白受体1敲除小鼠中比较了转铁蛋白受体1在发育和成人骨骼肌中的功能。结果显示,胚胎期小鼠骨骼肌缺失转铁蛋白受体1可导致骨骼肌严重萎缩和早期死亡,而成年骨骼肌缺失转铁蛋白受体1则不影响小鼠生存和糖代谢水平,但可导致骨骼肌萎缩和运动障碍,与去神经支配后骨骼肌萎缩表型类似。结果表明转铁蛋白受体1在控制肌肉发育和失神经引起的肌肉萎缩中起关键作用。实验已于201861日经北京基础医学研究所机构动物伦理委员会批准,批准号SYXK 2017-C023

https://orcid.org/0000-0001-8437-3194 (Hai-Tao Wu)

关键词: 肌肉, 神经支配, 肌萎缩, 铁, 臂丛神经, 信号, 铁转运, 运动障碍

Abstract: Previous studies demonstrate an accumulation of transferrin and transferrin receptor 1 (TfR1) in regenerating peripheral nerves. However, the expression and function of transferrin and TfR1 in the denervated skeletal muscle remain poorly understood. In this study, a mouse model of denervation was produced by complete tear of the left brachial plexus nerve. RNA-sequencing revealed that transferrin expression in the denervated skeletal muscle was upregulated, while TfR1 expression was downregulated. We also investigated the function of TfR1 during development and in adult skeletal muscles in mice with inducible deletion or loss of TfR1. The ablation of TfR1 in skeletal muscle in early development caused severe muscular atrophy and early death. In comparison, deletion of TfR1 in adult skeletal muscles did not affect survival or glucose metabolism, but caused skeletal muscle atrophy and motor functional impairment, similar to the muscular atrophy phenotype observed after denervation. These findings suggest that TfR1 plays an important role in muscle development and denervation-induced muscular atrophy. This study was approved by the Institutional Animal Care and Use Committee of Beijing Institute of Basic Medical Sciences, China (approval No. SYXK 2017-C023) on June 1, 2018.

Key words: brachial plexus nerve, innervation, iron, motor dysfunction, muscle atrophy, signal, skeletal muscle, transferrin