• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Human Molecular Genetics >Attenuated muscle regeneration is a key factor in dysferlin-deficient muscular dystrophy.
【24h】

Attenuated muscle regeneration is a key factor in dysferlin-deficient muscular dystrophy.

机译：肌肉再生减弱是dysferlin缺陷型肌营养不良症的关键因素。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Skeletal muscle requires an efficient and active membrane repair system to overcome the rigours of frequent contraction. Dysferlin is a component of that system and absence of dysferlin causes muscular dystrophy (dysferlinopathy) characterized by adult onset muscle weakness, high serum creatine kinase levels and a prominent inflammatory infiltrate. We have observed that dysferlinopathy patient biopsies show an excess of immature fibres and therefore investigated the role of dysferlin in muscle regeneration. Using notexin-induced muscle damage, we have shown that regeneration is attenuated in a mouse model of dysferlinopathy, with delayed removal of necrotic fibres, an extended inflammatory phase and delayed functional recovery. Satellite cell activation and myoblast fusion appear normal, but there is a reduction in early neutrophil recruitment in regenerating and also needle wounded muscle in dysferlin-deficient mice. Primary mouse dysferlinopathy myoblast cultures show reduced cytokine release upon stimulation, indicating that the secretion of chemotactic molecules is impaired. We suggest an extension to the muscle membrane repair model, where in addition to fusing patch repair vesicles with the sarcolemma dysferlin is also involved in the release of chemotactic agents. Reduced neutrophil recruitment results in incomplete cycles of regeneration in dysferlinopathy which combines with the membrane repair deficit to ultimately trigger dystrophic pathology. This study reveals a novel pathomechanism affecting muscle regeneration and maintenance in dysferlinopathy and highlights enhancement of the neutrophil response as a potential therapeutic avenue in these disorders.
机译：骨骼肌需要有效而活跃的膜修复系统来克服频繁收缩的严峻考验。 dysferlin是该系统的组成部分，dysferlin的缺乏会导致肌肉营养不良（dysferlinopathy），其特征是成年发作的肌肉无力，血清肌酸激酶水平高和明显的炎症浸润。我们已经观察到，dysferlinopathy患者的活组织检查显示未成熟纤维过多，因此研究了dysferlin在肌肉再生中的作用。使用notexin诱导的肌肉损伤，我们已经表明，在dysferlinopathy的小鼠模型中，再生减弱，坏死纤维的清除延迟，炎症期延长和功能恢复延迟。卫星细胞活化和成肌细胞融合似乎正常，但是在缺乏铁蛋白的小鼠中，再生中的中性粒细胞早期募集减少，并且针伤肌肉也减少。原发性小鼠dysferlinopathy成肌细胞培养物显示刺激后细胞因子释放减少，表明趋化分子的分泌受到损害。我们建议扩展到肌肉膜修复模型，其中除了将修补膜修复囊泡与肌膜dysferlin融合外，还参与趋化剂的释放。中性粒细胞募集的减少导致了铁蛋白缺乏症的再生循环不完全，这与膜修复缺陷结合在一起，最终引发营养不良性病理。这项研究揭示了一种新的病理机制，可影响dysferlinopathy中的肌肉再生和维持，并着重强调嗜中性粒细胞反应的增强作为这些疾病的潜在治疗途径。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号