Serrano Antonio L, Baeza-Raja Bernat, Perdiguero Eusebio, Jardí Mercè, Muñoz-Cánoves Pura
Program on Differentiation and Cancer, Center for Genomic Regulation (CRG) and Center for Neurodegenerative Diseases (CIBERNED), Pompeu Fabra University, Barcelona, Spain.
Cell Metab. 2008 Jan;7(1):33-44. doi: 10.1016/j.cmet.2007.11.011.
Skeletal muscles adapt to increasing workload by augmenting their fiber size, through mechanisms that are poorly understood. This study identifies the cytokine interleukin-6 (IL-6) as an essential regulator of satellite cell (muscle stem cell)-mediated hypertrophic muscle growth. IL-6 is locally and transiently produced by growing myofibers and associated satellite cells, and genetic loss of IL-6 blunted muscle hypertrophy in vivo. IL-6 deficiency abrogated satellite cell proliferation and myonuclear accretion in the preexisting myofiber by impairing STAT3 activation and expression of its target gene cyclin D1. The growth defect was indeed muscle cell intrinsic, since IL-6 loss also affected satellite cell behavior in vitro, in a STAT3-dependent manner. Myotube-produced IL-6 further stimulated cell proliferation in a paracrine fashion. These findings unveil a role for IL-6 in hypertrophic muscle growth and provide mechanistic evidence for the contribution of satellite cells to this process.
骨骼肌通过尚不明确的机制增大其纤维尺寸来适应不断增加的负荷。本研究确定细胞因子白细胞介素-6（IL-6）是卫星细胞（肌肉干细胞）介导的肥大性肌肉生长的关键调节因子。IL-6由生长中的肌纤维和相关卫星细胞局部短暂产生，IL-6基因缺失会减弱体内肌肉肥大。IL-6缺乏通过损害STAT3激活及其靶基因细胞周期蛋白D1的表达，消除了卫星细胞增殖和既有肌纤维中的肌核增加。生长缺陷确实是肌肉细胞内在性的，因为IL-6缺失也以STAT3依赖的方式影响体外卫星细胞行为。肌管产生的IL-6以旁分泌方式进一步刺激细胞增殖。这些发现揭示了IL-6在肥大性肌肉生长中的作用，并为卫星细胞对这一过程的贡献提供了机制证据。
