μ-Crystallin controls muscle function through thyroid hormone action
μ-Crystallin controls muscle function through thyroid hormone action
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DOI：
10.1096/fj.15-280933
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发表时间：
2016-05-01
期刊：
影响因子：
4.8
通讯作者：
Ono, Yusuke
中科院分区：
文献类型：
--
作者：
Seko, Daiki;Ogawa, Shizuka;Ono, Yusuke
MU-Crystallin(Crym)是一种甲状腺激素结合蛋白，在面肩肩周肌营养不良症患者的肌肉中异常上调，这是一种主要遗传的进行性肌病。然而，Crym在骨骼肌中的生理功能仍有待阐明。在本研究中，Crym在全身骨骼肌中优先表达。Crym基因敲除小鼠表现出显著的快速抽动糖酵解IIb型纤维肥大，导致Crym基因缺失小鼠的握力和高强度跑步能力增加。基因失活的Crym或通过siRNA介导的击倒阻断Crym可上调卫星细胞来源的肌管中快速糖酵解收缩纤维的基因表达。尽管Crym是非肌肉细胞中甲状腺激素活动的正调节因子，但Crym失活肌肉中的这些变化可以通过抑制甲状腺激素来挽救。结果表明，Crym是肌肉可塑性的重要调节因子，控制着肌肉纤维的代谢和收缩特性，因此，Crym的选择性失活可能成为肌肉萎缩疾病的潜在治疗靶点，如肌营养不良和与年龄相关的石膏减少症。
mu-Crystallin (Crym), a thyroid hormone-binding protein, is abnormally up-regulated in the muscles of patients with facioscapulohumeral muscular dystrophy, a dominantly inherited progressive myopathy. However, the physiologic function of Crym in skeletal muscle remains to be elucidated. In this study, Crym was preferentially expressed in skeletal muscle throughout the body. Crym-knockoutmice exhibited a significant hypertrophy of fast-twitch glycolytic type IIb fibers, causing an increase in grip strength and high intensity running ability in Crym-null mice. Genetic inactivation of Crym or blockade of Crym by siRNA-mediated knockdown up-regulated the gene expression of fast-glycolytic contractile fibers in satellite cell-derived myotubes in vitro. These alterations in Crym-inactivated muscle were rescued by inhibition of thyroid hormone, even though Crym is a positive regulator of thyroid hormone action in nonmuscle cells. The results demonstrated that Crym is a crucial regulator of muscle plasticity, controlling metabolic and contractile properties of myofibers, and thus the selective inactivation of Crym may be a potential therapeutic target for muscle-wasting diseases, such as muscular dystrophies and age-related sarcopenia.-Seko, D., Ogawa, S., Li, T.-S., Taimura, A., Ono, Y. mu-Crystallin controls muscle function through thyroid hormone action.