Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan; Department of Anesthesiology and Critical Care, Hiroshima University, Hiroshima, Japan.
Biochem Biophys Res Commun. 2024 Dec 10;737:150918. doi: 10.1016/j.bbrc.2024.150918. Epub 2024 Oct 28.
Skeletal muscle atrophy impairs quality of life and increases the risk of disease, but current methods for assessment of muscle mass have several limitations. We here investigated the urinary concentration of a fragment of the muscle protein titin as a potential biomarker for the early detection of skeletal muscle atrophy. Four mouse models with different atrophy pathways were studied: those of cardiotoxin-induced acute muscle injury, cast-induced muscle immobilization, lipopolysaccharide-induced sepsis, and streptozotocin-induced diabetes. In all four models, urinary titin levels increased early, concurrent with or preceding upregulation of the atrophy-related genes for atrogin-1 and MuRF-1. The increase in the urinary titin concentration was thus associated with initial muscle damage and the onset of proteolysis, rather than with late-stage muscle wasting. Our findings suggest that urinary titin is a promising biomarker for detection of the onset of skeletal muscle catabolism and prediction of the subsequent development of atrophy in different catabolic states. Noninvasive measurement of urinary titin may therefore allow the earlier detection of skeletal muscle proteolysis compared with conventional techniques.
骨骼肌萎缩会降低生活质量并增加患病风险，但目前评估肌肉量的方法存在一些局限性。我们在此研究了肌联蛋白片段在尿液中的浓度作为一种潜在的生物标志物，用于早期检测骨骼肌萎缩。研究了四种具有不同萎缩途径的小鼠模型：心肌毒素诱导的急性肌肉损伤、石膏固定诱导的肌肉失用、脂多糖诱导的败血症和链脲佐菌素诱导的糖尿病。在所有四种模型中，尿中titin 水平均早期升高，与 atrogin-1 和 MuRF-1 等与萎缩相关的基因上调同时或早于其上调。因此，尿 titin 浓度的增加与初始肌肉损伤和蛋白水解的开始有关，而不是与晚期肌肉消耗有关。我们的研究结果表明，尿 titin 是一种很有前途的生物标志物，可用于检测骨骼肌分解代谢的开始，并预测不同分解代谢状态下随后发生的萎缩。与传统技术相比，尿 titin 的非侵入性测量可能更早地检测到骨骼肌蛋白水解。
