Department of Medicine and Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Am J Pathol. 2013 Dec;183(6):1703-1709. doi: 10.1016/j.ajpath.2013.08.010. Epub 2013 Nov 11.
Xin is a striated muscle-specific protein that is localized to the myotendinous junction in skeletal muscle. However, in injured mouse muscle, Xin expression is up-regulated and observed throughout skeletal muscle fibers and within satellite cells. In this study, Xin was analyzed by immunofluorescent staining in skeletal muscle samples from 47 subjects with various forms of myopathy, including muscular dystrophies, inflammatory myopathies, mitochondrial/metabolic myopathy, and endocrine myopathy. Results indicate that Xin immunoreactivity is positively and significantly correlated (rs = 0.6175, P = <0.0001) with the severity of muscle damage, regardless of myopathy type. Other muscle damage measures also showed a correlation with severity [Xin actin-binding repeat-containing 2 (rs = -0.7108, P = 0.0006) and collagen (rs = 0.4683, P = 0.0783)]. However, because only Xin lacked immunoreactivity within the healthy muscle belly, any detectable immunoreactivity for Xin was indicative of muscle damage. We also investigated the expression of Xin within the skeletal muscle of healthy individuals subjected to damaging eccentric exercise. Consistent with our previously mentioned results, Xin immunoreactivity was increased 24 hours after exercise in damaged muscle fibers and within the activated muscle satellite cells. Taken together, these data demonstrate Xin as a useful biomarker of muscle damage in healthy individuals and in patients with myopathy. The strong correlation between the degree of muscle damage and Xin immunoreactivity suggests that Xin may be a suitable outcome measure to evaluate disease progression and treatment effects in clinical trials.
Xin 是一种横纹肌特异性蛋白，定位于骨骼肌的肌-腱连接处。然而，在受损的鼠肌肉中，Xin 的表达上调，并在整个骨骼肌纤维和卫星细胞中观察到。在这项研究中，通过免疫荧光染色分析了来自 47 名患有各种形式肌病的受试者的骨骼肌样本，包括肌营养不良症、炎性肌病、线粒体/代谢性肌病和内分泌性肌病。结果表明，无论肌病类型如何，Xin 免疫反应性与肌肉损伤的严重程度呈正相关(rs = 0.6175，P <0.0001)。其他肌肉损伤指标也与严重程度相关[Xin 肌动蛋白结合重复含 2(rs = -0.7108，P = 0.0006)和胶原蛋白(rs = 0.4683，P = 0.0783)]。然而，由于只有 Xin 在健康的肌腹中缺乏免疫反应性，因此任何可检测到的 Xin 免疫反应性都表明存在肌肉损伤。我们还研究了在经历破坏性离心运动的健康个体的骨骼肌中 Xin 的表达。与我们之前提到的结果一致，Xin 免疫反应性在受损的肌纤维和激活的肌肉卫星细胞中在运动后 24 小时增加。综上所述，这些数据表明 Xin 是健康个体和肌病患者肌肉损伤的有用生物标志物。肌肉损伤程度与 Xin 免疫反应性之间的强相关性表明，Xin 可能是一种合适的终点指标，可用于评估临床试验中的疾病进展和治疗效果。
