Novel roles of FKBP5 in muscle alteration induced by gravity change in mice
Novel roles of FKBP5 in muscle alteration induced by gravity change in mice
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DOI：
10.1016/j.bbrc.2016.09.126
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发表时间：
2016-10-21
影响因子：
3.1
通讯作者：
Kaji, Hiroshi
中科院分区：
文献类型：
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作者：
Shimoide, Takeshi;Kawao, Naoyuki;Kaji, Hiroshi
超重力和微重力分别引起骨骼肌肥大和萎缩。然而，重力变化调节肌肉质量的机制仍然不清楚。我们以前报道过，超重力通过前庭系统增加小鼠的肌肉质量。在这项研究中，我们进行了比较DNA微阵列分析的比目鱼肌从小鼠保持在1或3克的环境中有或没有前庭病变。在手术双侧前庭损伤后14天，通过使用离心机将小鼠保持在1g或3g环境中4周。FKBP 5作为一种基因被提取出来，其表达通过前庭系统被超重力增强。FKBP 5稳定过表达增加了小鼠成肌细胞C2 C12中Akt和p70 S6激酶（肌肉蛋白合成途径）和肌球蛋白重链（肌管基因）的磷酸化水平，但降低了肌蛋白降解相关基因atrogin-1和MuRF 1的mRNA水平。总之，我们首次证明FKBP 5是由超重通过前庭系统在小鼠的抗重力肌肉中诱导的。我们的数据表明，FKBP 5可能通过增强肌肉蛋白合成和肌管分化以及抑制肌肉蛋白降解来增加肌肉质量。(C)2016 Elsevier Inc. All rights reserved.
Skeletal muscle hypertrophy and wasting are induced by hypergravity and microgravity, respectively. However, the mechanisms by which gravity change regulates muscle mass still remain unclear. We previously reported that hypergravity increases muscle mass via the vestibular system in mice. In this study, we performed comparative DNA microarray analysis of the soleus muscle from mice kept in 1 or 3 g environments with or without vestibular lesions. Mice were kept in 1 g or 3 g environment for 4 weeks by using a centrifuge 14 days after surgical bilateral vestibular lesions. FKBP5 was extracted as a gene whose expression was enhanced by hypergravity through the vestibular system. Stable FKBP5 overexpression increased the phosphorylations of Akt and p70 S6 kinase (muscle protein synthesis pathway) and myosin heavy chain, a myotube gene, mRNA level in mouse myoblastic C2C12 cells, although it reduced the mRNA levels of atrogin-1 and MuRF1, muscle protein degradation-related genes. In conclusion, we first showed that FKBP5 is induced by hypergravity through the vestibular system in anti-gravity muscle of mice. Our data suggest that FKBP5 might increase muscle mass through the enhancements of muscle protein synthesis and myotube differentiation as well as an inhibition of muscle protein degradation in mice. (C) 2016 Elsevier Inc. All rights reserved.