Implication of satellite cell behaviors in capillary growth via VEGF expression-independent mechanism in response to mechanical loading in HeyL-null mice
Implication of satellite cell behaviors in capillary growth via VEGF expression-independent mechanism in response to mechanical loading in HeyL-null mice
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DOI：
10.1152/ajpcell.00343.2021
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发表时间：
2022-02-01
影响因子：
5.5
通讯作者：
Ogasawara, Riki
中科院分区：
文献类型：
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作者：
Ato, Satoru;Fukada, So-ichiro;Ogasawara, Riki
血管生成和肌肉卫星细胞（SC）介导的肌核增生被认为是收缩诱导的肌肉肥大的强大反应所必需的。此外，肌核和SCs在物理上都与毛细血管相邻，是骨骼肌中促血管生成因子（如VEGF）表达的主要部位。因此，在肌肉肥大过程中，通过活化SCs增加新的肌核可能在血管生成中起重要作用。然而，肌核数、毛细血管供应和血管生成因子之间的相关性尚未得到证实。Notch效应因子HeyL在骨骼肌的SC中特异性表达，并通过抑制MyoD在负荷过度诱导的肌肉肥大中对SC增殖至关重要。在这里，我们通过重新分析来自heyl敲除（KO）小鼠的骨骼肌，测试了SC在过载肌肉中添加新的肌核是否与血管生成适应有关，这些小鼠对SC增殖、肌核添加和过载诱导的肌肉肥大的反应减弱。再分析证实，增效剂消融后9周，HeyL-KO小鼠足底肌SC增殖和mynuclear增生减弱。有趣的是，在野生型（WT）小鼠中观察到的毛细血管与纤维比率的增加在HeyL-KO小鼠中受到损害。在WT和HeyL-KO小鼠中，VEGFA和VEGFB的表达在过载反应中同样增加。此外，血管生成负调节因子TSP-1的表达模式在WT和HeyL-KO小鼠之间也没有变化。总之，这些结果表明，SCs激活-肌核增生在负荷诱导的肌肉肥大过程中，通过独立的血管生成调节因子在血管生成中起着至关重要的作用。
Angiogenesis and muscle satellite cell (SC)-mediated myonuclear accretion are considered essential for the robust response of contraction-induced muscle hypertrophy. Moreover, both myonucleus and SCs are physically adjacent to capillaries and are the major sites for the expression of proangiogenic factors, such as VEGF, in the skeletal muscle. Thus, events involving the addition of new myonuclei via activation of SCs may play an important role in angiogenesis during muscle hypertrophy. However, the relevance among myonuclei number, capillary supply, and angiogenesis factor is not demonstrated. The Notch effector HeyL is specifically expressed in SCs in the skeletal muscle and is crucial for SC proliferation by inhibiting MyoD in overload-induced muscle hypertrophy. Here, we tested whether the addition of new myonuclei by SC in overloaded muscle is associated with angiogenic adaptation by reanalyzing skeletal muscle from HeyL-knockout (KO) mice, which show blunted responses of SC proliferation, myonucleus addition, and overload-induced muscle hypertrophy. Reanalysis confirmed blunted SC proliferation and myonuclear accretion in the plantaris muscle of HeyL-KO mice 9 wk after synergist ablation. Interestingly, the increase in capillary-to -fiber ratio observed in wild-type (WT) mice was impaired in HeyL-KO mice. In both WT and HeyL-KO mice, the expression of VEGFA and VEGFB was similarly increased in response to overload. In addition, the expression pattern of TSP-1, a negative regulator of angiogenesis, was also not changed between WT and HeyL-KO mice. Collectively, these results suggest that SCs activation-myonuclear accretion plays a crucial role in angiogenesis during overload-induced muscle hypertrophy via independent of angiogenesis regulators.