Modulating Fibro/Adipogenic Precursors to Prevent Adipogenic Replacement of Muscle

摘要。 成功的肌肉再生需要多个细胞之间精心的细胞编排 细胞群来移除和替换受损的纤维。破坏这种编排会导致 肌肉变性和肌纤维的纤维化或脂肪形成替代。这种现象 特别是在肌营养不良症中普遍存在，其中进行性肌肉损失导致严重的 虚弱和早期生命损失。因此，越来越需要了解细胞 种群及其相互作用，有助于肌纤维再生，但可能导致 纤维化或脂肪形成的替代。该项目旨在了解 导致肌纤维损失和肌肉损伤的细胞相互作用受损的潜在机制 2B型肢带型肌营养不良症的无力和预防这种无力的测试方法 损伤这种理解将有助于开发新的靶向治疗方法， 阻止这种和其他肌营养不良症的疾病进展， 有效的治疗选择。

ABSTRACT. Successful muscle regeneration requires an elaborate cellular choreography between multiple cell populations to remove and replace damaged fibers. Disruption of this choreography leads to muscle degeneration and fibrotic or adipogenic replacement of myofibers. This phenomenon is particularly prevalent in muscular dystrophies, where progressive muscle loss leads to severe debilitation and early loss of life. Hence, there is growing need to understand the cell populations and their interactions which contribute to myofiber regeneration, but can lead to fibrotic or adipogenic replacement when gone awry. This project aims to understand the mechanism underlying impaired cellular interactions leading to myofiber loss and muscle weakness in limb girdle muscular dystrophy type 2B and test approaches to prevent this impairment. This understanding will help develop novel targeted therapeutic approaches to arrest disease progression in this and other muscular dystrophies that are currently without effective treatment options.