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Macrophage-released ADAMTS1 promotes muscle stem cell activation
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Macrophage-released ADAMTS1 promotes muscle stem cell activation
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Journal Article
Macrophage-released ADAMTS1 promotes muscle stem cell activation
2017
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ ADAMTS1 Protein - metabolism
/ Animals
/ Humanities and Social Sciences
/ Humans
/ Injuries
/ Muscle Development - genetics
/ Muscle, Skeletal - metabolism
/ Muscle, Skeletal - physiopathology
/ Mutation
/ Receptor, Notch1 - metabolism
/ Rodents
/ Satellite Cells, Skeletal Muscle - metabolism
/ Science
