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|Title:||Effects of the Systemic Environment in Health and Disease on Skeletal Muscle Development|
|Department:||Medical Sciences (Division of Physiology/Pharmacology)|
|Abstract:||Children with cystic fibrosis (CF) show signs of systemic inflammation. Studies suggest that systemic inflammation is related to increased protein breakdown, which, in turn, is related to lower fat-free mass in CF patients. However, the direct implications of systemic inflammation on skeletal muscle tissue development are unknown. The focus of this thesis was to elucidate the effect of systemic factors from children with CF and healthy children on C2C12 myoblast myogenesis in vitro, and to assess whether systemic factors altered by exercise can modulate myogenesis, or provide an anti-inflammatory protection from an inflammatory mediator. Our first study demonstrated that myoblasts treated with pooled CF serum had higher levels of proliferation, as measured by the total number of nuclei, compared to control serum. There was no exercise effect on proliferation in CF, while post-exercise serum from healthy controls showed an increase in proliferation compared to resting serum. In our next study, we confirmed that myoblasts treated with individual samples of CF serum had greater proliferation than control serum. Differentiation, as measured by the myonuclei fusion index, was decreased in myoblasts treated with CF serum. No exercise effect was observed for proliferation or differentiation. Our final study illustrated that an inflammatory mediator, lipopolysaccharide (LPS), decreased differentiation, as measured by myonuclei fusion index, in myoblasts treated with CF resting serum but increased differentiation in myoblasts treated with control resting serum. Post-exercise recovery from children with CF reversed the effects of LPS, while exercise and recovery serum from healthy controls blunted the effects of LPS. Collectively, our data suggest that systemic factors can have an effect on myogenesis, with differences observed between CF and control serum. Although post-exercise serum did not consistently affect myogenesis, anti-inflammatory effects are evidenced by the protection these factors provided from the effects of an inflammatory mediator.|
|Appears in Collections:||Open Access Dissertations and Theses|
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|Nguyen, Thanh - PhD Thesis.pdf||Nguyen, Thanh - PhD Thesis||7.36 MB||Adobe PDF||View/Open|
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