Department of Cell Physiology, The Jikei University School of Medicine, Nishishinbashi, Minato-ku, Tokyo, Japan.
PLoS One. 2023 Aug 15;18(8):e0289185. doi: 10.1371/journal.pone.0289185. eCollection 2023.
Early detection of skeletal muscle atrophy is important to prevent further muscle weakness. However, there are few non-invasive biomarkers for skeletal muscle atrophy. Recent studies have reported that the N-terminal fragment (N-titin) of titin, a giant sarcomeric protein, is detected in the urine of patients with muscle damage. In this study, we hypothesized that urinary N-titin would be a potential early biomarker of skeletal muscle atrophy in mice caused by sciatic nerve denervation. Male mice were randomly divided into control and denervation groups, and urinary N-titin levels were assessed daily for 9 days using an enzyme-linked immunosorbent assay system. Despite reduced titin protein levels in atrophic muscles 10 days after denervation, cleaved N-titin fragments were not increased in the urine of mice with denervation-induced muscle atrophy. Furthermore, we found no uptake of Evans blue dye from the extracellular space into the cytoplasm in atrophic muscles, suggesting that the sarcomeric membrane is intact in those muscles. The present results suggest that cleaved N-titin in the urine is not suitable as an early biomarker of skeletal muscle atrophy.
早期发现骨骼肌萎缩对于预防肌肉进一步虚弱很重要。然而，目前用于检测骨骼肌萎缩的非侵入性生物标志物很少。最近的研究报告称，肌节巨型蛋白肌联蛋白的 N 端片段（N-肌联蛋白）可在肌肉损伤患者的尿液中检测到。在这项研究中，我们假设尿 N-肌联蛋白可能是坐骨神经切断引起的小鼠骨骼肌萎缩的潜在早期生物标志物。雄性小鼠被随机分为对照组和去神经组，使用酶联免疫吸附测定系统每天评估尿 N-肌联蛋白水平 9 天。尽管去神经后 10 天萎缩肌肉中的肌联蛋白水平降低，但去神经诱导的肌肉萎缩小鼠的尿液中未增加切割的 N-肌联蛋白片段。此外，我们在萎缩肌肉中未发现从细胞外空间摄取伊文思蓝染料进入细胞质，这表明这些肌肉中的肌节膜是完整的。目前的结果表明，尿液中的切割 N-肌联蛋白不适合作为骨骼肌萎缩的早期生物标志物。
