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Abstract：
The progressive degeneration of the skeletal musculature in Duchenne muscular dystrophy is accompanied by reactive myofibrosis, fat substitution, and chronic inflammation. Fibrotic changes and reduced tissue elasticity correlate with the loss in motor function in this X-chromosomal disorder. Thus, although dystrophinopathies are due to primary abnormalities in the DMD gene causing the almost-complete absence of the cytoskeletal Dp427-M isoform of dystrophin in voluntary muscles, the excessive accumulation of extracellular matrix proteins presents a key histopathological hallmark of muscular dystrophy. Animal model research has been instrumental in the characterization of dystrophic muscles and has contributed to a better understanding of the complex pathogenesis of dystrophinopathies, the discovery of new disease biomarkers, and the testing of novel therapeutic strategies. In this article, we review how mass-spectrometry-based proteomics can be used to study changes in key components of the endomysium, perimysium, and epimysium, such as collagens, proteoglycans, matricellular proteins, and adhesion receptors. The mdx-4cv mouse diaphragm displays severe myofibrosis, making it an ideal model system for large-scale surveys of systematic alterations in the matrisome of dystrophic fibers. Novel biomarkers of myofibrosis can now be tested for their appropriateness in the preclinical and clinical setting as diagnostic, pharmacodynamic, prognostic, and/or therapeutic monitoring indicators.
摘要：
Duchenne肌营养不良症的骨骼肌系统的进行性变性伴随着反应性肌纤维化，脂肪替代，慢性炎症。在这种X染色体疾病中，纤维化变化和组织弹性降低与运动功能丧失有关。因此，尽管肌萎缩蛋白病是由于DMD基因的原发性异常导致在随意肌中几乎完全不存在肌萎缩蛋白的细胞骨架Dp427-M同工型，细胞外基质蛋白的过度积累是肌营养不良症的重要组织病理学标志。动物模型的研究已经在表征营养不良的肌肉，并有助于更好地了解肌萎缩蛋白病的复杂发病机理，新的疾病生物标志物的发现，以及新治疗策略的测试。在这篇文章中,我们回顾了基于质谱的蛋白质组学如何用于研究内膜关键成分的变化，周围铯，和epimysium，如胶原蛋白，蛋白聚糖,体细胞蛋白质，和粘附受体。mdx-4cv小鼠隔膜显示严重的肌纤维化，使其成为一个理想的模型系统，用于大规模调查营养不良纤维组成的系统变化。现在可以测试肌纤维化的新型生物标志物在临床前和临床环境中作为诊断的适当性。药效学，预后，和/或治疗监测指标。
