TWEAK and TRAF6 regulate skeletal muscle atrophy.
TWEAK and TRAF6 regulate skeletal muscle atrophy.
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调整和TRAF6调节骨骼肌萎缩。
DOI：
10.1097/mco.0b013e328351c3fc
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发表时间：
2012-05
影响因子：
3.1
通讯作者：
Paul PK
中科院分区：
文献类型：
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作者：
Kumar A;Bhatnagar S;Paul PK
本文就TWEAK和TRAF 6在骨骼肌萎缩中的作用及其机制进行综述。已知促炎细胞因子在许多慢性疾病状态中介导肌肉萎缩。然而，它们在废用条件下骨骼肌质量损失中的作用才刚刚开始阐明。此外，在不同的萎缩条件下，导致骨骼肌中各种分解代谢途径激活的初始信号事件也不太清楚。TWEAK-Fn 14系统现已被鉴定为骨骼肌萎缩的新型诱导剂。成人骨骼肌表达最低水平的Fn 14（真正的TWEAK受体）。特定的萎缩条件，如去神经支配，固定，或卸载快速诱导Fn 14的表达，导致TWEAK诱导的骨骼肌中各种蛋白水解途径的激活。最近的研究还表明，TRAF 6的表达和活性在不同的肌肉萎缩模型中增加。TRAF 6的肌肉特异性消融抑制响应于饥饿、去神经支配或癌症恶病质的萎缩程序的诱导。此外，TWEAK似乎还通过TRAF 6依赖性机制激活一些分解代谢信号。最近的研究发现TWEAK和TRAF 6是骨骼肌萎缩的新调节因子。这些蛋白质可能在未来的治疗中用作预防和/或治疗肌萎缩的分子靶点。
The purpose of this review is to discuss the roles and mechanisms of action of TWEAK and TRAF6 in skeletal muscle atrophy. Proinflammatory cytokines are known to mediate muscle atrophy in many chronic disease states. However, their role in the loss of skeletal muscle mass in disuse conditions has just begun to be elucidated. Further, the initial signaling events leading to the activation of various catabolic pathways in skeletal muscle under different atrophic conditions are also less well understood. The TWEAK-Fn14 system has now been identified as a novel inducer of skeletal muscle wasting. Adult skeletal muscles express minimal levels of Fn14, the bona fide TWEAK receptor. Specific conditions of atrophy such as denervation, immobilization, or unloading rapidly induce the expression of Fn14 leading to TWEAK-induced activation of various proteolytic pathways in skeletal muscle. Recent studies have also demonstrated that the expression and activity of TRAF6 are increased in distinct models of muscle atrophy. Muscle-specific ablation of TRAF6 inhibits the induction of atrophy program in response to starvation, denervation, or cancer cachexia. Moreover, TWEAK also appears to activate some catabolic signaling through TRAF6-dependent mechanisms. Recent findings have uncovered TWEAK and TRAF6 as novel regulators of skeletal muscle atrophy. These proteins should potentially be used as molecular targets for prevention and/or treatment of muscular atrophy in future therapies.