Contribution of satellite cells to IGF-I induced hypertrophy of skeletal muscle.
Contribution of satellite cells to IGF-I induced hypertrophy of skeletal muscle.
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DOI：
10.1046/j.1365-201x.1999.00618.x
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发表时间：
1999-12
期刊：
影响因子：
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通讯作者：
E. Barton-Davis;D. Shoturma;H. Sweeney
中科院分区：
文献类型：
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作者：
E. Barton-Davis;D. Shoturma;H. Sweeney
胰岛素样生长因子I（IGF-I）在促进骨骼肌生长中起关键作用。当通过病毒介导的基因转移将IGF-I引入小鼠后肢肌肉时，与未处理的对照相比，IGF-I的局部过表达产生肌肉质量和强度的显著增加（Barton-Davis et al. 1998）。我们提出，这种功能性肥大主要是由于卫星细胞的激活导致肌肉再生增加。为了测试卫星细胞是否在介导IGF-I的肥大效应中是必不可少的，我们使用γ辐射来破坏卫星细胞的增殖能力。对成年C57 BL/6雄性小鼠的右后肢进行以下处理之一：（1）仅2，500 rad伽马辐射，（2）仅病毒介导的IGF-I基因转移，（3）2，500 rad伽马辐射加病毒介导的IGF-I基因转移，或（4）无干预作为对照。治疗后约4个月，从两个后肢取趾长伸肌（EDL）进行力学和形态学测量。伽马射线治疗显著阻止了肌肉的正常生长。当与IGF-I治疗组合时，大约一半的IGF-I效应被γ辐射治疗阻止。这表明IGF-I诱导的肥大的剩余一半是由于对成体肌纤维的旁分泌/自分泌作用。因此，这些数据与IGF-I通过卫星细胞活化和增加分化肌纤维中蛋白质合成的组合诱导肌肉肥大的机制一致。
Insulin-like growth factor I (IGF-I) is critical in promoting growth of skeletal muscle. When IGF-I is introduced into mouse hindlimb muscles by viral-mediated gene transfer, local overexpression of IGF-I produces significant increases in muscle mass and strength compared with untreated controls (Barton-Davis et al. 1998). We have proposed that this functional hypertrophy is primarily owing to the activation of satellite cells which leads to increased muscle regeneration. In order to test if satellite cells are essential in mediating the hypertrophic effects of IGF-I, we used gamma radiation to destroy the proliferative capacity of satellite cells. The right hindlimbs of adult C57BL/6 male mice were subjected to one of the following treatments: (1) 2,500 rad gamma radiation only, (2) viral-mediated gene transfer of IGF-I only, (3) 2,500 rad gamma radiation plus viral-mediated gene transfer of IGF-I, or (4) no intervention as a control. Approximately 4 months after treatment, the extensor digitorum longus muscles (EDL) from both hindlimbs were removed for mechanical and morphological measurements. Treatment with gamma radiation significantly prevented normal growth of the muscle. When combined with IGF-I treatment, approximately half of the IGF-I effect was prevented by gamma radiation treatment. This suggests that the remaining half of IGF-I induced hypertrophy is owing to paracrine/autocrine effects on the adult myofibres. Thus, these data are consistent with a mechanism by which IGF-I induced muscle hypertrophy via a combination of satellite cell activation and increasing protein synthesis in differentiated myofibres.