Local Vibration Stimuli Induce Mechanical Stress-Induced Factors and Facilitate Recovery From Immobilization-Induced Oxidative Myofiber Atrophy in Rats
Local Vibration Stimuli Induce Mechanical Stress-Induced Factors and Facilitate Recovery From Immobilization-Induced Oxidative Myofiber Atrophy in Rats
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DOI：
10.3389/fphys.2019.00759
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发表时间：
2019-06
影响因子：
4
通讯作者：
F. Usuki;M. Fujimura;A. Nakamura;J. Nakano;M. Okita;I. Higuchi
中科院分区：
文献类型：
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作者：
F. Usuki;M. Fujimura;A. Nakamura;J. Nakano;M. Okita;I. Higuchi
肌肉萎缩可由卸载压力引起，如微重力环境或石膏固定。这种废用性肌肉萎缩的治疗方法及其潜在的机制尚不完全清楚。在这里，我们研究了局部振动刺激对制动所致骨骼肌萎缩的治疗效果。将左后肢打上石膏1周，造成大鼠骨骼肌氧化性肌纤维萎缩，而比目鱼骨骼肌无肌病改变。在固定期末摘除石膏后，使用手持振动按摩器对萎缩的后肢足底筋膜进行振动刺激(90 Hz，15min)，每天一次。2周后解剖大鼠，对比目鱼肌肌纤维横截面积进行定量分析。结果表明，与未经处理的固定化样品相比，振动可显著恢复废用性肌肉萎缩。此外，与未经振动处理的固定化样品相比，振动处理抑制了纤维从慢纤维类型到快纤维类型的转变。Western blotting对机械应激诱导因子的分析显示，机械生长因子(MGF)、系统性胰岛素样生长因子I和机械转导蛋白YAP1在未处理的固定比目鱼肌中的表达减少，而振动刺激恢复了它们的表达。YAP1Ser127的磷酸化水平没有改变，导致振动处理的固定比目鱼肌的p-YAP1/YAP1比值没有改变。结果表明，振动刺激能有效地恢复固定化所致的YAP1通路失活。在振动处理的固定比目鱼肌中，ERK 1/2的磷酸化增强，而AKT的磷酸化不增强。此外，振动刺激恢复了固定化诱导的成对框转录因子PAX7的下调，PAX7是肌肉卫星细胞再生肌肉发生的关键因子。我们的结果表明，周期性振动刺激有效地激活了卫星细胞，并通过上调MGF和YAP1的表达，促进了固定诱导的氧化性肌纤维萎缩的恢复。
Muscle atrophy can be caused by unloading stress such as microgravity environments or cast immobilization. Therapies for such disuse muscle atrophy and their underlying mechanisms are incompletely understood. Here, we investigated the therapeutic effects of local vibration stimulation on immobilization-induced skeletal muscle atrophy. A rat model was made by placing the left hindlimb in a cast for 1 week, leading to oxidative myofiber atrophy without myopathic changes in soleus skeletal muscle. Vibration stimulus (90 Hz, 15 min) to the plantar fascia of the atrophic hindlimb was performed once a day using a hand-held vibration massager after removal of a cast at the end of the immobilization period. After 2 weeks, rats were dissected, and quantitative analysis of the cross-sectional areas of soleus myofibers was performed. The results revealed that vibration induced significant recovery from disuse muscle atrophy, compared with untreated immobilized samples. Furthermore, vibration treatment suppressed the fiber transition from slow to fast fiber types compared with vibration-untreated immobilized samples. Western blotting analyses of mechanical stress-induced factors revealed that the expression of mechano-growth factor (MGF), systemic insulin-like growth factor I, and the mechanotransduction protein, Yes-associated protein 1 (YAP1), was decreased in untreated immobilized soleus muscle, whereas vibration stimulation restored their expression. No change in the level of phosphorylation of YAP1Ser127 was observed, leading to no change in p-YAP1/YAP1 ratio in vibration-treated immobilized soleus muscle. The results indicate that vibration stimulus is effective to restore immobilization-induced inactivation of YAP1 pathway. Phosphorylation of ERK 1/2, but not AKT, was enhanced in vibration-treated immobilized soleus muscle. Furthermore, vibration stimuli restored immobilization-induced downregulation of the paired box transcription factor, PAX7, a critical factor for regenerative myogenesis in muscle satellite cells. Our results indicate that cyclic vibration stimuli are effective in activating satellite cells and facilitate recovery from immobilization-induced oxidative myofiber atrophy through upregulation of MGF and YAP1.