Macrophage-released ADAMTS1 promotes muscle stem cell activation.
Macrophage-released ADAMTS1 promotes muscle stem cell activation.
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DOI：
10.1038/s41467-017-00522-7
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发表时间：
2017-09-22
影响因子：
16.6
通讯作者：
Feldman BJ
中科院分区：
文献类型：
--
作者：
Du H;Shih CH;Wosczyna MN;Mueller AA;Cho J;Aggarwal A;Rando TA;Feldman BJ
肌肉干细胞（称为卫星细胞）的协调激活对出生后肌肉生长和再生至关重要。肌肉干细胞龛是调节卫星细胞激活状态的中心，但协调这种调节的特定细胞外信号知之甚少。在这里，我们表明，肌肉损伤部位的巨噬细胞通过表达Adamts1诱导卫星细胞活化。体内巨噬细胞中Adamts1的过表达足以增加卫星细胞活化并改善年轻小鼠的肌肉再生。我们证明，NOTCH1是ADAMTS1金属蛋白酶活性的靶点，其减少Notch信号传导，导致卫星细胞活化增加。这些结果将Adamts1鉴定为卫星细胞活化的有效细胞外调节剂，并且对于理解肌肉损伤后卫星细胞活性和再生的调节具有重要意义。卫星细胞对骨骼肌的生长和再生至关重要。在这里，作者表明，作为对肌肉损伤的反应，巨噬细胞分泌Adamts1，其通过调节Notch1信号传导诱导卫星细胞活化。
Coordinated activation of muscle stem cells (known as satellite cells) is critical for postnatal muscle growth and regeneration. The muscle stem cell niche is central for regulating the activation state of satellite cells, but the specific extracellular signals that coordinate this regulation are poorly understood. Here we show that macrophages at sites of muscle injury induce activation of satellite cells via expression of Adamts1. Overexpression of Adamts1 in macrophages in vivo is sufficient to increase satellite cell activation and improve muscle regeneration in young mice. We demonstrate that NOTCH1 is a target of ADAMTS1 metalloproteinase activity, which reduces Notch signaling, leading to increased satellite cell activation. These results identify Adamts1 as a potent extracellular regulator of satellite cell activation and have significant implications for understanding the regulation of satellite cell activity and regeneration after muscle injury. Satellite cells are crucial for growth and regeneration of skeletal muscle. Here the authors show that in response to muscle injury, macrophages secrete Adamts1, which induces satellite cell activation by modulating Notch1 signaling.
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