Neuromuscular Center at The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Muscle Nerve. 2013 May;47(5):731-9. doi: 10.1002/mus.23669. Epub 2013 Mar 29.
Recent in vitro studies suggest that CAPN3 deficiency leads initially to accelerated myofiber formation followed by depletion of satellite cells (SC). In normal muscle, up-regulation of miR-1 and miR-206 facilitates transition from proliferating SCs to differentiating myogenic progenitors.
We examined the histopathological stages, Pax7 SC content, and muscle-specific microRNA expression in biopsy specimens from well-characterized LGMD 2A patients to gain insight into disease pathogenesis.
Three distinct stages of pathological changes were identified that represented the continuum of the dystrophic process from prominent inflammation with necrosis and regeneration to prominent fibrosis, which correlated with age and disease duration. Pax7-positive SCs were highest in the fibrotic group and correlated with down-regulation of miR-1, miR-133a, and miR-206.
These observations, and other published reports, are consistent with microRNA dysregulation leading to inability of Pax7-positive SCs to transit from proliferation to differentiation. This results in impaired regeneration and fibrosis.
最近的体外研究表明，CAPN3 缺乏症最初会导致肌纤维形成加速，随后卫星细胞 (SC) 耗竭。在正常肌肉中，miR-1 和 miR-206 的上调有助于增殖的 SC 向分化的成肌祖细胞转化。
我们检查了经过充分特征描述的 LGMD 2A 患者活检标本中的组织病理学阶段、Pax7 SC 含量和肌肉特异性 microRNA 表达，以深入了解疾病发病机制。
确定了三个不同的病理变化阶段，代表了从明显炎症伴坏死和再生到明显纤维化的营养不良过程的连续过程，这与年龄和疾病持续时间相关。Pax7 阳性 SC 在纤维化组中最高，并与 miR-1、miR-133a 和 miR-206 的下调相关。
这些观察结果和其他已发表的报告一致，表明 microRNA 失调导致 Pax7 阳性 SC 无法从增殖过渡到分化。这导致再生和纤维化受损。
