Skeletal muscle fiber type conversion during the repair of mouse soleus: potential implications for muscle healing after injury.

Abstract

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.