Browsing School, Graduate by Title "Sarcolemmal repair and recovery from contraction-induced skeletal muscle injury"
Now showing items 1-1 of 1
Sarcolemmal repair and recovery from contraction-induced skeletal muscle injurySkeletal muscle injuries from lengthening contractions are common and can lead to varying levels of limitation of function. The goal of my research has been to study the mechanisms that mediate injury and recovery, by examining muscles injured by a few large-strain lengthening contractions (LSI; Large-strain injury), or by numerous small-strain lengthening contractions (SSI; Small-strain injury). I studied injury and recovery in the tibialis anterior (TA) muscle of the rat, to test the hypothesis that myogenesis is not necessary for recovery from LSI. I assessed contractile force, sarcolemmal repair and myogenesis, and inhibited activation of myosatellite cells through X-irradiation, to study recovery without myogenesis. After LSI, TA muscles recovered most of their contractile force within 7 days and repaired their sarcolemmae, but did not show significant myogenesis. TA muscles after SSI, recovered over 14 days and did not repair their sarcolemmae, but showed significant myogenesis. Furthermore, X-irradiated TA muscles recovered normally from LSI but not SSI. These data support the hypothesis that recovery from LSI involves sarcolemmal repair but not myogenesis.;I next studied recovery from LSI and SSI in control mice and in mice lacking the sarcolemmal repair protein, dysferlin, to test the hypothesis that myogenesis can mediate recovery from LSI when membrane repair is impaired. Using methods adapted from those used for rats, I found that control mice recover from LSI and SSI in a manner similar to the rat. Dysferlin-deficient mice recovered from LSI in a manner similar to SSI in the rat, through myogenesis. Dysferlin-deficient muscles were also infiltrated by more inflammatory cells after both LSI and SSI, compared to controls. My results support the hypothesis that myogenesis mediates recovery from LSI when membrane repair is impaired by the absence of dysferlin and suggest that dysferlin may be involved in controlling inflammation after injury. I conclude that the predominant mechanism involved in recovery from contraction-induced injuries varies with the nature of the injury and the state of the muscle. These findings provide insight into the mechanisms that underlie injury, and recovery from injury and also provide insight into the pathogenesis of muscle diseases linked to dysferlin.