Nitric oxide sustains long-term skeletal muscle regeneration by regulating fate of satellite cells via signaling pathways requiring Vangl2 and cyclic GMP.
Nitric oxide sustains long-term skeletal muscle regeneration by regulating fate of satellite cells via signaling pathways requiring Vangl2 and cyclic GMP.
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DOI：
10.1002/stem.783
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发表时间：
2012-02
期刊：
影响因子：
5.2
通讯作者：
Clementi, Emilio
中科院分区：
文献类型：
--
作者：
Buono, Roberta;Vantaggiato, Chiara;Pisa, Viviana;Azzoni, Emanuele;Bassi, Maria Teresa;Brunelli, Silvia;Sciorati, Clara;Clementi, Emilio
卫星细胞是肌源性前体细胞，其在肌肉损伤时增殖、活化和分化以维持成人骨骼肌的再生能力;在此过程中，它们通过循环后代恢复静止来自我更新。这种机制虽然在生理条件下有效，但不能防止病理学中卫星细胞的耗竭，例如发生多轮损伤的肌营养不良症。在这里，我们描述了一氧化氮，一个重要的信号分子在成人骨骼肌，卫星细胞的维护，离体研究分离的肌纤维和在体内使用α-肌聚糖空小鼠模型的营养不良和心脏毒素诱导的重复损伤模型的关键作用。一氧化氮刺激卫星细胞增殖的途径依赖于cGMP的产生。此外，它增加了cGMP非依赖性途径中Pax 7 +/Myf 5 −细胞的数量，需要增强Vangl 2的表达，Vangl 2是Wnt非经典途径中涉及的平面细胞极性途径的成员。一氧化氮诱导的卫星细胞自我更新能力增强足以延迟重复急性和慢性损伤期间卫星细胞池的减少，有利于肌肉再生;在α-肌聚糖缺失型营养不良小鼠中，它还持续减缓疾病进展。这些结果确定了一氧化氮作为卫星细胞维持中的关键信使，扩展了Vangl 2依赖性Wnt非经典途径在肌生成中的意义，并指示了优化肌营养不良症的基于一氧化氮的疗法的新策略。干细胞2012; 30：197-209.
Satellite cells are myogenic precursors that proliferate, activate, and differentiate on muscle injury to sustain the regenerative capacity of adult skeletal muscle; in this process, they self-renew through the return to quiescence of the cycling progeny. This mechanism, while efficient in physiological conditions does not prevent exhaustion of satellite cells in pathologies such as muscular dystrophy where numerous rounds of damage occur. Here, we describe a key role of nitric oxide, an important signaling molecule in adult skeletal muscle, on satellite cells maintenance, studied ex vivo on isolated myofibers and in vivo using the α-sarcoglycan null mouse model of dystrophy and a cardiotoxin-induced model of repetitive damage. Nitric oxide stimulated satellite cells proliferation in a pathway dependent on cGMP generation. Furthermore, it increased the number of Pax7+/Myf5− cells in a cGMP-independent pathway requiring enhanced expression of Vangl2, a member of the planar cell polarity pathway involved in the Wnt noncanonical pathway. The enhanced self-renewal ability of satellite cells induced by nitric oxide is sufficient to delay the reduction of the satellite cell pool during repetitive acute and chronic damages, favoring muscle regeneration; in the α-sarcoglycan null dystrophic mouse, it also slowed disease progression persistently. These results identify nitric oxide as a key messenger in satellite cells maintenance, expand the significance of the Vangl2-dependent Wnt noncanonical pathway in myogenesis, and indicate novel strategies to optimize nitric oxide-based therapies for muscular dystrophy. Stem Cells 2012; 30:197–209.
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DOI：
10.1073/pnas.0805514105
发表时间：
2008-12-09
影响因子：
11.1
作者：
Colussi, Claudia;Mozzetta, Chiara;Gaetano, Carlo
通讯作者：
Gaetano, Carlo
影响因子：
7.8
作者：
Deponti, Daniela;Francois, Stephanie;Brunelli, Silvia
通讯作者：
Brunelli, Silvia
影响因子：
56.9
作者：
Brack, Andrew S.;Conboy, Michael J.;Rando, Thomas A.
通讯作者：
Rando, Thomas A.
影响因子：
12.4
作者：
通讯作者：
--
影响因子：
5.5
作者：
Drenning, Jason A.;Lira, Vitor A.;Criswell, David S.
通讯作者：
Criswell, David S.