细胞生物学
整合素
再生(生物学)
干细胞
生物
蛋白激酶B
骨骼肌
肌营养不良
信号转导
细胞
内分泌学
生物化学
遗传学
作者
Michelle Rozo,Liangji Li,Chen‐Ming Fan
出处
期刊:Nature Medicine
[Springer Nature]
日期:2016-07-04
卷期号:22 (8): 889-896
被引量:161
摘要
Interactions between stem cells and their microenvironment, or niche, are essential for stem cell maintenance and function. Our knowledge of the niche for the skeletal muscle stem cell, i.e., the satellite cell (SC), is incomplete. Here we show that β1-integrin is an essential niche molecule that maintains SC homeostasis, and sustains the expansion and self-renewal of this stem cell pool during regeneration. We further show that β1-integrin cooperates with fibroblast growth factor 2 (Fgf2), a potent growth factor for SCs, to synergistically activate their common downstream effectors, the mitogen-activated protein (MAP) kinase Erk and protein kinase B (Akt). Notably, SCs in aged mice show altered β1-integrin activity and insensitivity to Fgf2. Augmenting β1-integrin activity with a monoclonal antibody restores Fgf2 sensitivity and improves regeneration after experimentally induced muscle injury. The same treatment also enhances regeneration and function of dystrophic muscles in mdx mice, a model for Duchenne muscular dystrophy. Therefore, β1-integrin senses the SC niche to maintain responsiveness to Fgf2, and this integrin represents a potential therapeutic target for pathological conditions of the muscle in which the stem cell niche is compromised.
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