To improve muscle healing upon injury, it is of importance to understand the interplay of key signaling pathways during muscle regeneration. To study this, mice were injected with cardiotoxin (CTX) or PBS in the Tibialis Anterior muscle and were sacrificed 2, 5 and 12 days upon injection. The time points represent different phases of the regeneration process, i.e. destruction, repair and remodeling, respectively. Two days upon CTX-injection, p-mTORC1 signaling and stress markers such as BiP and p-ERK1/2 were upregulated. Phospho-ERK1/2 and p-mTORC1 peaked at d5, while BiP expression decreased towards PBS levels. Phospho-FOXO decreased 2 and 5 days following CTX-injection, indicative of an increase in catabolic signaling. Furthermore, CTX-injection induced a shift in the fiber type composition, characterized by an initial loss in type IIa fibers at d2 and at d5. At d5, new type IIb fibers appeared, whereas type IIa fibers were recovered at d12. To conclude, CTX-injection severely affected key modulators of muscle metabolism and histology. These data provide useful information for the development of strategies that aim to improve muscle molecular signaling and thereby recovery.

为了改善受伤后的肌肉愈合，了解肌肉再生过程中关键信号通路的相互作用非常重要。为了研究这一点，小鼠在胫骨前肌中注射了心脏毒素 (CTX) 或 PBS，并在注射后 2、5 和 12 天处死。时间点分别代表再生过程的不同阶段，即破坏、修复和重塑。注射 CTX 两天后，p-mTORC1 信号和压力标记物（如 BiP 和 p-ERK1/2）上调。Phospho-ERK1/2 和 p-mTORC1 在第 5 天达到峰值，而 BiP 表达向着 PBS 水平下降。Phospho-FOXO 在注射 CTX 后 2 天和 5 天下降，表明分解代谢信号增加。此外，CTX 注射引起了纤维类型组成的变化，特征是在 d2 和 d5 时 IIa 型光纤的初始损耗。在 d5 时，出现了新的 IIb 型纤维，而在 d12 时恢复了 IIa 型纤维。总而言之，CTX 注射严重影响了肌肉代谢和组织学的关键调节剂。这些数据为制定旨在改善肌肉分子信号从而恢复的策略提供了有用的信息。