Level of muscle regeneration in limb-girdle muscular dystrophy type 2I relates to genotype and clinical severity
Level of muscle regeneration in limb-girdle muscular dystrophy type 2I relates to genotype and clinical severity
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DOI：
10.1186/2044-5040-1-31
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发表时间：
2011-01-01
期刊：
影响因子：
4.9
通讯作者：
Vissing, John
中科院分区：
文献类型：
--
作者：
Krag, Thomas O.;Hauerslev, Simon;Vissing, John
背景资料：肌肉再生和持续退化之间的平衡是一种关系，极大地影响了肌肉萎缩症的进展。许多因素可能会影响肌肉再生，但更多的信息之间的关系基因型，临床严重程度和再生能力是needed.Methods：从胫骨前肌肌肉活检，冷冻切片染色一般组织病理学和免疫组织化学评价。使用Student's unpaired t-test.Results：我们发现，所有患肢带型肌营养不良症2 I型（LGMD 2 I）的患者都有大量的内部有核纤维，这是以前再生的标志。肌肉特异性发育蛋白如新生肌球蛋白重链（nMHC）和肌细胞生成素的表达水平与临床严重程度相关。此外，我们发现大多数nMHC阳性纤维在L276 I突变的复合杂合子患者中未对utrophin呈阳性染色，这表明这些患者的主要再生形式是纤维修复而不是新纤维的形成。双重染色显示，许多较小的nMHC阳性纤维对于针对α-肌营养不良蛋白聚糖上的糖基化的抗体呈阳性，这表明这种糖基化可能是肌肉再生的结果。LGMD 2 I严重受累的患者具有高水平的肌肉变性，这导致高再生率，但这不足以改变变性和再生之间的不平衡，最终导致肌肉萎缩关于肌肉再生的水平和速度以及再生途径的潜在障碍的详细信息应该用于涉及卫星细胞活化的未来疗法。
Background: The balance between muscle regeneration and ongoing degeneration is a relationship that greatly influences the progression of muscular dystrophy. Numerous factors may influence the muscle regeneration, but more information about the relationship between genotype, clinical severity and the ability to regenerate is needed.Methods: Muscle biopsies were obtained from the tibialis anterior muscle, and frozen sections were stained for general histopathological and immunohistological evaluation. Differences between groups were considered statistical significant at P < 0.05 using Student's unpaired t-test.Results: We found that all patients with limb-girdle muscular dystrophy type 2I (LGMD2I) had a large number of internally nucleated fibers, a sign of previous regeneration. The level of expression of muscle-specific developmental proteins, such as neonatal myosin heavy chain (nMHC) and myogenin, was related to the clinical severity. Additionally, we found that the majority of nMHC-positive fibers did not stain positively for utrophin in patients who were compound heterozygous for the L276I mutation, suggesting that the predominant form of regeneration in these patients is fiber repair rather than formation of new fibers. Double staining showed that many smaller nMHC-positive fibers were positive for antibodies against the glycosylation on a-dystroglycan, suggesting that such glycosylation may be a result of muscle regeneration.Conclusion: Severely affected patients with LGMD2I have a high level of muscle degeneration, which leads to a high rate of regeneration, but this is insufficient to change the imbalance between degeneration and regeneration, ultimately leading to progressive muscle wasting. Detailed information regarding the level and rate of muscle regeneration and potential obstructions of the regenerative pathway should be of use for future therapies involving satellite-cell activation.