Matsuura Tetsuya, Li Yong, Giacobino Jean-Paul, Fu Freddie H, Huard Johnny
Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Orthop Res. 2007 Nov;25(11):1534-40. doi: 10.1002/jor.20451.
We used a mouse model of cardiotoxin injury to examine fiber type conversion during muscle repair. We evaluated the soleus muscles of 37 wild-type mice at 2, 4, 8, and 12 weeks after injury. We also used antibodies (fMHC and sMHC) against fast and slow myosin heavy chain to classify the myofibers into three categories: fast-, slow-, and mixed (hybrid)-type myofibers (myofibers expressing both fMHC and sMHC). Our results revealed an increase in the percentage of slow-type myofibers and a decrease in the percentage of fast-type myofibers during the repair process. The percentage of hybrid-type myofibers increased 2 weeks after injury, then gradually decreased over the following 6 weeks. Similarly, our analysis of centronucleated myofibers showed an increase in the percentage of slow-type myofibers and decreases in the percentages of fast- and hybrid-type myofibers. We also investigated the relationship between myofiber type conversion and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha). The expression of both PGC-1alpha protein, which is expressed in both the nucleus and the cytoplasm of regenerating myofibers, and sMHC protein increased with time after cardiotoxin injection, but we observed no significant differential expression of fMHC protein in regenerating muscle fibers during muscle repair. PGC-1alpha-positive myofibers underwent fast to slow myofiber type conversion during the repair process. These results suggest that PGC-1alpha contributes to myofiber type conversion after muscle injury and that this phenomenon could influence the recovery of the injured muscle.
我们使用心脏毒素损伤的小鼠模型来研究肌肉修复过程中的纤维类型转换。我们在损伤后2周、4周、8周和12周评估了37只野生型小鼠的比目鱼肌。我们还使用针对快肌球蛋白重链和慢肌球蛋白重链的抗体（fMHC和sMHC）将肌纤维分为三类：快肌型、慢肌型和混合（杂交）型肌纤维（同时表达fMHC和sMHC的肌纤维）。我们的结果显示，在修复过程中慢肌型肌纤维的百分比增加，快肌型肌纤维的百分比减少。杂交型肌纤维的百分比在损伤后2周增加，然后在接下来的6周逐渐下降。同样，我们对中心核肌纤维的分析显示，慢肌型肌纤维的百分比增加，快肌型和杂交型肌纤维的百分比减少。我们还研究了肌纤维类型转换与过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）之间的关系。在再生肌纤维的细胞核和细胞质中均有表达的PGC-1α蛋白和sMHC蛋白的表达均随着心脏毒素注射后的时间而增加，但在肌肉修复过程中，我们未观察到再生肌纤维中fMHC蛋白有明显的差异表达。在修复过程中，PGC-1α阳性肌纤维经历了从快肌型到慢肌型的转换。这些结果表明，PGC-1α有助于肌肉损伤后的肌纤维类型转换，并且这种现象可能影响受损肌肉的恢复。
