The role of myostatin in muscle wasting: an overview.

The role of myostatin in muscle wasting: an overview.
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DOI:
10.1007/s13539-011-0035-5
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发表时间:
2011-09
影响因子:
8.9
通讯作者:
Springer, Jochen
Springer, Jochen
中科院分区:
医学1区
文献类型:
--
作者:
Elkina, Yulia;von Haehling, Stephan;Anker, Stefan D.;Springer, Jochen

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肌生长抑制素是一种主要在骨骼肌中表达的细胞外细胞因子,在肌肉质量的负调控中起重要作用。在与激活素IIB受体结合后,肌肉生长抑制素可以启动几种不同的信号级联反应,导致atrogenes上调和肌生成重要基因的下调。肌肉大小是通过肌肉生长抑制素信号与胰岛素样生长因子1/磷脂酰肌醇3-激酶/Akt通路的复杂相互作用来调节的,该通路负责增加肌肉中蛋白质的合成。因此,肌肉重量的调节是一个肌肉生长抑制素发挥核心作用的过程,但其作用机制和信号级联尚不完全清楚。在与不同疾病(如癌症、心力衰竭、HIV)相关的恶病质期间,肌肉萎缩的发病机制中观察到肌生长抑制素上调。因此,肌生长抑制素信号的表征是恶病质治疗发展的一个远景方向。目前的综述涵盖了目前关于肌肉生长抑制素信号通路导致肌肉萎缩的知识,以及通过调节肌肉生长抑制素和/或其恶病质下游靶点的治疗方法的现状。
Myostatin is an extracellular cytokine mostly expressed in skeletal muscles and known to play a crucial role in the negative regulation of muscle mass. Upon the binding to activin type IIB receptor, myostatin can initiate several different signalling cascades resulting in the upregulation of the atrogenes and downregulation of the important for myogenesis genes. Muscle size is regulated via a complex interplay of myostatin signalling with the insulin-like growth factor 1/phosphatidylinositol 3-kinase/Akt pathway responsible for increase in protein synthesis in muscle. Therefore, the regulation of muscle weight is a process in which myostatin plays a central role but the mechanism of its action and signalling cascades are not fully understood. Myostatin upregulation was observed in the pathogenesis of muscle wasting during cachexia associated with different diseases (i.e. cancer, heart failure, HIV). Characterisation of myostatin signalling is therefore a perspective direction in the treatment development for cachexia. The current review covers the present knowledge about myostatin signalling pathways leading to muscle wasting and the state of therapy approaches via the regulation of myostatin and/or its downstream targets in cachexia.
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