Rahman Fasih Ahmad, Campbell Troy, Bloemberg Darin, Chapman Sarah, Quadrilatero Joe
Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
Muscles. 2023 Sep 15;2(3):299-316. doi: 10.3390/muscles2030023.
Skeletal muscle is a complex tissue comprising multinucleated and post-mitotic cells (i.e., myofibers). Given this, skeletal muscle must maintain a fine balance between growth and degradative signals. A major system regulating the remodeling of skeletal muscle is autophagy, where cellular quality control is mediated by the degradation of damaged cellular components. The accumulation of damaged cellular material can result in elevated apoptotic signaling, which is particularly relevant in skeletal muscle given its post-mitotic nature. Luckily, skeletal muscle possesses the unique ability to regenerate in response to injury. It is unknown whether a relationship between autophagy and apoptotic signaling exists in injured skeletal muscle and how autophagy deficiency influences myofiber apoptosis and regeneration. In the present study, we demonstrate that an initial inducible muscle-specific autophagy deficiency does not alter apoptotic signaling following cardiotoxin injury. This finding is presumably due to the re-establishment of ATG7 levels following injury, which may be attributed to the contribution of a functional gene from satellite cells. Furthermore, the re-expression of ATG7 resulted in virtually identical regenerative potential. Overall, our data demonstrate that catastrophic injury may "reset" muscle gene expression via the incorporation of nuclei from satellite cells.
骨骼肌是一种复杂的组织，由多核的有丝分裂后细胞（即肌纤维）组成。鉴于此，骨骼肌必须在生长信号和降解信号之间保持精细的平衡。调节骨骼肌重塑的一个主要系统是自噬，其中细胞质量控制是通过受损细胞成分的降解来介导的。受损细胞物质的积累会导致凋亡信号升高，鉴于骨骼肌有丝分裂后的性质，这在骨骼肌中尤为重要。幸运的是，骨骼肌具有受伤后再生的独特能力。目前尚不清楚在受伤的骨骼肌中自噬与凋亡信号之间是否存在关系，以及自噬缺陷如何影响肌纤维凋亡和再生。在本研究中，我们证明最初诱导的肌肉特异性自噬缺陷在心脏毒素损伤后不会改变凋亡信号。这一发现可能是由于损伤后ATG7水平的重新建立，这可能归因于卫星细胞中一个功能基因的贡献。此外，ATG7的重新表达导致了几乎相同的再生潜力。总体而言，我们的数据表明，严重损伤可能通过整合卫星细胞的细胞核来“重置”肌肉基因表达。
