Macrophage-released ADAMTS1 promotes muscle stem cell activation

被引：104

作者：

Du, Hongqing ^{[1
]}

Shih, Chung-Hsuan ^{[1
]}

Wosczyna, Michael N. ^{[2
]}

Mueller, Alisa A. ^{[2
,3
]}

Cho, Joonseok ^{[1
]}

Aggarwal, Abhishek ^{[1
]}

Rando, Thomas A. ^{[2
,3
,4
]}

Feldman, Brian J. ^{[1
,3
,5
,6
]}

机构：

[1] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

[3] Stanford Univ, Program Canc Biol, Stanford, CA 94305 USA

[4] Stanford Univ, Paul F Glenn Labs Biol Aging, Stanford, CA 94305 USA

[5] Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA

[6] Stanford Univ, Program Regenerat Med, Stanford, CA 94305 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

SATELLITE CELL; SELF-RENEWAL; REGENERATION; MAINTENANCE; QUIESCENCE; INJURY; NICHE; REQUIREMENT; DISINTEGRIN; MYOGENESIS;

D O I：

10.1038/s41467-017-00522-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

共 32 条

[1] A Disintegrin-like and Metalloprotease (Reprolysin-type) with Thrombospondin Type 1 Motif (ADAMTS) Superfamily: Functions and Mechanisms [J].