Skeletal muscle is one of the largest functional tissues in the human body; it is highly plastic and responds dramatically to anabolic and catabolic stimuli, including weight training and malnutrition, respectively. Excessive loss of muscle mass, or atrophy, is a common symptom of many disease states with severe impacts on prognosis and quality of life. TNF-like weak inducer of apoptosis (TWEAK) and its cognate receptor, fibroblast growth factor-inducible 14 (Fn14) are an emerging cytokine signaling pathway in the pathogenesis of muscle atrophy. Upregulation of TWEAK and Fn14 has been described in a number of atrophic and injured muscle states; however, it remains unclear whether they are contributing to the degenerative or regenerative aspect of muscle insults. The current review focuses on the expression and apparent downstream outcomes of both TWEAK and Fn14 in a range of catabolic and anabolic muscle models. Apparent changes in the signaling outcomes of TWEAK-Fn14 activation dependent on the relative expression of both the ligand and the receptor are discussed as a potential source of divergent TWEAK-Fn14 downstream effects. This review proposes both a physiological and pathological model of TWEAK-Fn14 signaling. Further research is needed on the switch between these states to develop therapeutic interventions for this pathway.

骨骼肌是人体最大的功能组织之一。它具有很高的可塑性，并且对同化和分解代谢刺激（包括体重训练和营养不良）有显着反应。肌肉质量过度丧失或萎缩是许多疾病状态的常见症状，会对预后和生活质量产生严重影响。TNF样的凋亡微弱诱导剂（TWEAK）及其相关受体，成纤维细胞生长因子诱导型14（Fn14）是肌肉萎缩发病机理中新兴的细胞因子信号传导途径。TWEAK和Fn14的上调在多种萎缩和受伤的肌肉状态中都有描述。然而，尚不清楚它们是否在肌肉损伤的退化或再生方面起作用。当前的审查集中在一系列分解代谢和合成代谢肌肉模型中，TWEAK和Fn14的表达和明显的下游结果。TWEAK-Fn14激活的信号转导结果的明显变化取决于配体和受体的相对表达，被认为是不同的TWEAK-Fn14下游效应的潜在来源。这篇评论提出了TWEAK-Fn14信号传导的生理和病理模型。需要进一步研究这些状态之间的转换，以开发针对该途径的治疗性干预措施。TWEAK-Fn14激活的信号转导结果的明显变化取决于配体和受体的相对表达，被认为是不同的TWEAK-Fn14下游效应的潜在来源。这篇评论提出了TWEAK-Fn14信号传导的生理和病理模型。需要进一步研究这些状态之间的转换，以开发针对该途径的治疗性干预措施。TWEAK-Fn14激活的信号转导结果的明显变化取决于配体和受体的相对表达，被认为是不同的TWEAK-Fn14下游效应的潜在来源。这篇评论提出了TWEAK-Fn14信号传导的生理和病理模型。需要进一步研究这些状态之间的转换，以开发针对该途径的治疗性干预措施。