AMP-activated Protein Kinase Stimulates Warburg-like Glycolysis and Activation of Satellite Cells during Muscle Regeneration
AMP-activated Protein Kinase Stimulates Warburg-like Glycolysis and Activation of Satellite Cells during Muscle Regeneration
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DOI：
10.1074/jbc.m115.665232
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发表时间：
2015-10-30
影响因子：
4.8
通讯作者：
Du, Min
中科院分区：
文献类型：
--
作者：
Fu, Xing;Zhu, Mei-Jun;Du, Min
卫星细胞是骨骼肌内主要的肌源性干细胞，是肌肉再生不可缺少的细胞。卫星细胞在很大程度上保持静止，但在肌肉损伤时迅速激活，然后衍生的肌源性细胞融合以修复受损的肌纤维或形成新的肌纤维。然而，引起代谢活化的机制，肌肉损伤后卫星细胞活化不可分割的一步，尚未确定。我们发现，非经典的Sonic Hedgehog（Shh）通路在肌肉损伤后迅速激活，激活AMPK并诱导卫星细胞中的Warburg样糖酵解。AMPK α 1是卫星细胞中表达的主要AMPK α亚型，卫星细胞中AMPK α 1缺乏会损害其在肌肉再生过程中的活化和肌源性分化。激活非经典Shh的药物促进卫星细胞的增殖，但由于卫星细胞特异性AMPK α 1敲除，这种增殖被取消。总之，AMPK α 1是连接非经典Shh通路与卫星细胞中Warburg样糖酵解的关键介质，这是卫星激活和肌肉再生所必需的。
Satellite cells are the major myogenic stem cells residing inside skeletal muscle and are indispensable for muscle regeneration. Satellite cells remain largely quiescent but are rapidly activated in response to muscle injury, and the derived myogenic cells then fuse to repair damaged muscle fibers or form new muscle fibers. However, mechanisms eliciting metabolic activation, an inseparable step for satellite cell activation following muscle injury, have not been defined. We found that a non-canonical Sonic Hedgehog (Shh) pathway is rapidly activated in response to muscle injury, which activates AMPK and induces a Warburg-like glycolysis in satellite cells. AMPK alpha 1 is the dominant AMPK alpha isoform expressed in satellite cells, and AMPK alpha 1 deficiency in satellite cells impairs their activation and myogenic differentiation during muscle regeneration. Drugs activating noncanonical Shh promote proliferation of satellite cells, which is abolished because of satellite cell-specific AMPK alpha 1 knock-out. Taken together, AMPK alpha 1 is a critical mediator linking noncanonical Shh pathway to Warburg-like glycolysis in satellite cells, which is required for satellite activation and muscle regeneration.