Influence of hypoxic stimulation on angiogenesis and satellite cells in mouse skeletal muscle.

Influence of hypoxic stimulation on angiogenesis and satellite cells in mouse skeletal muscle.
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DOI:
10.1371/journal.pone.0207040
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Miyata H
Miyata H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nagahisa H;Miyata H

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我们在之前的研究中明确了低氧训练促进骨骼肌血管生成,但骨骼肌血管生成的机制尚不清楚。在这项研究中,我们研究了缺氧暴露对不同年龄骨骼肌血管生成和代谢特征的影响,其中活性氧和一氧化氮的产生可能不同。将10周龄和20月龄小鼠分为对照组(N)、持续缺氧组(H)和间歇缺氧组(IH)。H组连续5天接受16% O2缺氧,IH组在光照期每隔1小时进行16% O2缺氧,连续5天。缺氧暴露完成后,立即切除比目鱼肌和腓肠肌,利用实时RT-PCR检测血管生成和卫星细胞相关基因的mRNA表达。免疫组化法测定肌纤维类型组成、肌纤维面积、卫星细胞数、毛细血管密度。H组幼鱼比目鱼肌肌纤维面积减少,卫星细胞活化相关MyoD、MHCe、BDNF mRNA表达显著升高。另一方面,在老比目鱼肌中,H组nNOS和VEGF-A mRNA的表达及毛细血管密度均显著升高。在腓肠肌浅部,卫星细胞分泌的血管生成因子FGF2 mRNA表达在年轻IH组显著升高。此外,我们还发现,在比目鱼肌中VEGF-A mRNA的表达与nNOS mRNA的表达、腓肠肌浅部eNOS mRNA的表达呈正相关。这些数据表明,年龄、缺氧暴露方式和肌肉代谢特征相关,导致血管生成有显著差异。
We clarified in our previous study that hypoxic training promotes angiogenesis in skeletal muscle, but the mechanism of angiogenesis in skeletal muscle remains unknown. In this study, we investigated the influence of differences in hypoxia exposure on angiogenesis in skeletal muscles at differing ages and metabolic characteristics at which the production of reactive oxygen species and nitric oxide may differ. Ten-week-old (young) and 20-month-old (old) mice were separated into control (N), continuous hypoxia (H), and intermittent hypoxia (IH) groups. The H group was exposed to 16% O2 hypoxia for 5 days and the IH group was exposed to 16% O2 hypoxia at one-hour intervals during the light period for 5 days. After completion of hypoxia exposure, the soleus and gastrocnemius muscles were immediately excised, and mRNA expression of angiogenesis- and satellite cell-related genes was investigated using real-time RT-PCR. In addition, muscle fiber type composition, muscle fiber area, number of satellite cells, and capillary density were measured immunohistochemically. In the young soleus muscle, the muscle fiber area was decreased in the H group, and mRNA expression of satellite cell activation-related MyoD, MHCe, and BDNF was significantly increased. On the other hand, in the old soleus muscle, nNOS and VEGF-A mRNA expression, and the capillary density were significantly increased in the H group. In the superficial portion of the gastrocnemius, mRNA expression of FGF2, an angiogenic factor secreted by satellite cells, was significantly increased in the young IH group. In addition, a positive correlation between VEGF-A mRNA expression and nNOS mRNA expression in the soleus muscle and eNOS mRNA expression in the superficial portion of the gastrocnemius was noted. These data demonstrated that age, hypoxia exposure method and muscle metabolic characteristics are related, which results in significant differences in angiogenesis.
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