中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (8): 1293-1303.doi: 10.4103/1673-5374.189195

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

失神经支配快肌和慢肌萎缩早期的miRNA靶向信号通路

  

  • 出版日期:2016-08-31 发布日期:2016-08-31
  • 基金资助:
    国家自然科学基金(81101365, 81171722, 81000805)

miRNA targeted signaling pathway in the early stage of denervated fast and slow muscle atrophy

Gang Li*, #, Qing-shan Li#, Wen-bin Li, Jian Wei, Wen-kai Chang, Zhi Chen, Hu-yun Qiao, Ying-wei Jia, Jiang-hua Tian, Bing-sheng Liang   

  1. Department of Orthopedics, Second Affliated Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China
  • Online:2016-08-31 Published:2016-08-31
  • Contact: Gang Li, ligang.shanxi@hotmail.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81101365, 81171722 and 81000805.

摘要:

引发失神经支配快肌和慢肌萎缩的机制可能存在差异,而miRNAs 可能高度参与失神经支配骨骼肌病理生理进程。实验切除了雌性成年SD大鼠1cm右侧坐骨神经建立失神经支配模型。应用miRNA 微阵列分析失神经后1个月的失神经支配早期,模型大鼠典型慢肌(比目鱼肌)和快肌(胫骨前肌)miRNA表达谱。结果发现miR-206, miR-195, miR-23a和miR-30e 是失神经支配慢肌向快肌转换的关键调节因子。通过分析信号通路网络,实验发现了一些被这些miRNA调节的靶点:p38 MAPK, Pax3/ Pax7, HDAC4, IGF1/PI3K /Akt/mTOR, FoxO信号通路,实验结果为理解失神经支配骨骼肌病理生理机制提供了更多证据。

orcid: 0000-0001-7530-0866 (Gang Li)

关键词: miRNA, 表达谱, 失神经支配骨骼肌, 基因功能, 信号通路

Abstract: Denervation often results in skeletal muscle atrophy. Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy. At the epigenetic level, miRNAs are thought to be highly involved in the pathophysiological progress of denervated muscles. We used miRNA microarrays to determine miRNA expression profiles from a typical slow muscle (soleus muscle) and a typical fast muscle (tibialis anterior muscle) at an early denervation stage in a rat model. Results showed that miR-206, miR-195, miR-23a, and miR-30e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles. Additionally, certain miRNA molecules (miR-214, miR-221, miR-222, miR-152, miR-320, and Let-7e) could be key regulatory factors in the denervated atrophy process involved in fast muscle. Analysis of signaling pathway networks revealed the miRNA molecules that were responsible for regulating certain signaling pathways, which were the fnal targets (e.g., p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/mTOR pathway regulates atrogin-1 and MuRF1 expression via FoxO phosphorylation). Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.

Key words: nerve regeneration, microRNA, expression profile, denervated skeletal muscle, gene functions, signaling pathways, neural regeneration