Muscle satellite cells are normally quiescent but are rapidly activated following muscle damage. Here, we investigated whether damaged myofibers influence the activation of satellite cells. Our findings revealed that satellite cells are directly activated by damaged-myofiber-derived factors (DMDFs). DMDFs induced satellite cells to enter the cell cycle; however, the cells stayed at the G1 phase and did not undergo S phase, and these cells were reversible to the quiescent-like state. Proteome analysis identified metabolic enzymes, including GAPDH, as DMDFs, whose recombinant proteins stimulated the activation of satellite cells. Satellite cells pre-exposed to the DMDFs demonstrated accelerated proliferation ex vivo. Treatment with recombinant GAPDH prior to muscle injury promoted expansion of the satellite cell population in vivo. Thus, our results indicate that DMDFs are not only a set of biomarkers for muscle damage, but also act as moonlighting proteins involved in satellite cell activation at the initial step of muscle regeneration.

肌肉卫星细胞通常是静止的，但在肌肉损伤后会迅速激活。在这里，我们调查了受损的肌纤维是否会影响卫星细胞的激活。我们的发现表明，卫星细胞直接由受损的肌纤维衍生因子（DMDF）激活。DMDF诱导卫星细胞进入细胞周期。然而，这些细胞停留在G1期而未经历S期，并且这些细胞可逆转至静止状。蛋白质组分析确定了包括GAPDH在内的代谢酶为DMDF，其重组蛋白刺激了卫星细胞的活化。卫星细胞预先暴露于证实加速扩散的DMDFs体外。重组GAPDH在肌肉损伤前的治疗促进了体内卫星细胞的扩增。因此，我们的结果表明，DMDFs不仅是一组肌肉损伤的生物标志物，而且在肌肉再生的初始阶段还充当着参与卫星细胞活化的月光蛋白。