Attenuation of autophagy impacts on muscle fibre development, starvation induced stress and fibre regeneration following acute injury.
Attenuation of autophagy impacts on muscle fibre development, starvation induced stress and fibre regeneration following acute injury.
复制标题
DOI：
10.1038/s41598-018-27429-7
复制
发表时间：
2018-06-13
影响因子：
4.6
通讯作者：
Patel K
中科院分区：
文献类型：
--
作者：
Paolini A;Omairi S;Mitchell R;Vaughan D;Matsakas A;Vaiyapuri S;Ricketts T;Rubinsztein DC;Patel K
自噬已被认为是许多骨骼肌疾病发生的一个主要因素。然而，它在骨骼肌稳态中的作用仍在不断发展。我们检查了小鼠模型Atg16L1的骨骼肌结构，其中自噬减弱，但重要的是仍然存在。我们发现Atg16L1小鼠的肌纤维比野生型小鼠小，证明了该过程在这些细胞生长中的作用。我们发现，在急性饥饿的初始阶段，自噬的轻微衰减会导致肌肉损失加速。此外，我们发现，与野生型相比，Atg16L1小鼠在心脏毒素（CTX）介导的损伤后骨骼肌的再生速度较慢。最后，我们发现自噬控制着肌膜的完整性。CTX肌肉损伤后，自噬减弱使肌纤维更容易被循环免疫球蛋白浸润。这些纤维内化了肌营养不良蛋白和nNOS。重要的是，这些纤维能够恢复肌营养不良蛋白和nNOS的定位，并且不会死亡。总之，这些研究揭示了骨骼肌纤维应对损伤的能力，并建立了自噬微调与骨骼肌再生之间的联系。
Autophagy has been implicated as a major factor in the development of a number of diseases of skeletal muscle. However, its role in skeletal muscle homeostasis is still evolving. We examined skeletal muscle architecture in a mouse model, Atg16L1, where autophagy is attenuated but importantly still present. We show that muscle fibres from Atg16L1 mice were smaller than wild-type counterparts, proving a role for this process in the growth of these cells. We show that mild attenuation of autophagy results in accelerated muscle loss during the initial phase of acute starvation. Furthermore, we show that regeneration of skeletal muscle following cardiotoxin (CTX) mediated injury is slower in the Atg16L1 mouse compared to wild-type. Lastly, we show that autophagy controls the integrity of the sarcolemma. Attenuated autophagy makes muscle fibres more susceptible to infiltration by circulating immunoglobulins following muscle injury with CTX. These fibres internalise dystrophin and nNOS. Importantly these fibres are able to restore dystrophin and nNOS localisation and do not die. In conclusion, these studies shed new light into the ability of skeletal muscle fibres to cope with injury and establish a link between the fine-tuning of autophagy and skeletal muscle regeneration.
登录
查看更多内容
影响因子：
4.9
作者：
Allamand V;Briñas L;Richard P;Stojkovic T;Quijano-Roy S;Bonne G
通讯作者：
Bonne G
影响因子：
2.4
作者：
Harris, JB;Vater, R;Cullen, MJ
通讯作者：
Cullen, MJ
影响因子：
3.5
作者：
Carmignac, Virginie;Svensson, Martina;Durbeej, Madeleine
通讯作者：
Durbeej, Madeleine
影响因子：
3.3
作者：
Mizushima, N;Yamamoto, A;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
23.9
作者：
Crist, Colin G.;Montarras, Didier;Buckingham, Margaret
通讯作者：
Buckingham, Margaret