Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (7): 1308-1316.doi: 10.4103/1673-5374.301024

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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).

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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