PDF(Pubmed)
Abstract：
BACKGROUND: Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined.
RESULTS: Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter.
CONCLUSIONS: These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.
RESULTS: Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter.
CONCLUSIONS: These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.
摘要：
背景：卫星细胞是主要负责骨骼肌再生能力的组织特异性干细胞。卫星细胞的功能和维持受到外在和内在机制的调节，包括泛素-蛋白酶体系统,这是维持蛋白质稳态的关键。在这种情况下，研究表明，泛素连接酶NEDD4-1靶向转录因子PAX7进行蛋白酶体依赖性降解，在体外促进肌肉分化。尽管如此，NEDD4-1是否是再生肌肉中卫星细胞功能所必需的还有待确定。
结果：使用条件基因消融，我们显示NEDD4-1损失，特别是在卫星细胞群中，损害肌肉再生，导致整个肌肉大小的显着减少。在细胞层面,NEDD4-1-空肌肉祖细胞表现出增殖和分化能力的显着降低，有助于直径减小的肌纤维的形成。
结论：这些结果表明，NEDD4-1的表达对于体内适当的肌肉再生至关重要，并表明它可以在多个水平上控制卫星细胞功能。
结果：使用条件基因消融，我们显示NEDD4-1损失，特别是在卫星细胞群中，损害肌肉再生，导致整个肌肉大小的显着减少。在细胞层面,NEDD4-1-空肌肉祖细胞表现出增殖和分化能力的显着降低，有助于直径减小的肌纤维的形成。
结论：这些结果表明，NEDD4-1的表达对于体内适当的肌肉再生至关重要，并表明它可以在多个水平上控制卫星细胞功能。
