IL-13 mediates the recruitment of reserve cells for fusion during IGF-1-induced hypertrophy of human myotubes
IL-13 mediates the recruitment of reserve cells for fusion during IGF-1-induced hypertrophy of human myotubes
复制标题
DOI：
10.1242/jcs.03371
复制
发表时间：
2007-02-15
影响因子：
4
通讯作者：
Mouly, Vincent
中科院分区：
文献类型：
--
作者：
Jacquemin, Virginie;Butler-Browne, Gillian Sandra;Mouly, Vincent
胰岛素样生长因子-1(IGF-1)被证明可以诱导骨骼肌肥大，防止肌肉质量随着年龄的增长而减少，并改善营养不良小鼠的肌肉表型。我们以前建立了IGF-1诱导的人肌管肥大模型，在该模型中，肥大的特征不仅是肌管大小和肌球蛋白含量的增加，而且还包括为融合而招募的储备细胞的增加。在这里，我们描述了IGF-1诱导肥大的新机制，证明了IGF-1信号只作用于肌管，而不是储备细胞，在转录因子NFATc2的控制下，导致IL-13的分泌，继而招募储备细胞进行分化和融合。此外，我们还发现，IGF-1还通过Akt向肌管发出信号，通过(1)激活mTOR-p70S6K-S6途径和抑制GSK-3β途径来刺激蛋白质代谢，这两个途径都参与了蛋白质翻译的控制，以及(2)抑制Foxo1-阿托金-1蛋白质降解途径。
Insulin-like growth factor-1 (IGF-1) has been shown to induce skeletal muscle hypertrophy, to prevent the loss of muscle mass with ageing and to improve the muscle phenotype of dystrophic mice. We previously developed a model of IGF-1-induced hypertrophy of human myotubes, in which hypertrophy was not only characterized by an increase in myotube size and myosin content but also by an increased recruitment of reserve cells for fusion. Here, we describe a new mechanism of IGF-1-induced hypertrophy by demonstrating that IGF-1 signals exclusively to myotubes but not to reserve cells, leading, under the control of the transcription factor NFATc2, to the secretion of IL-13 that will secondly recruit reserve cells for differentiation and fusion. In addition, we show that IGF-1 also signals to myotubes to stimulate protein metabolism via Akt by (1) activating the mTOR-p70S6K-S6 pathway and inhibiting GSK-3 beta, both involved in the control of protein translation, and (2) inhibiting the Foxo1-atrogin-1 protein degradation pathway.