The effect of exercise on soluble factors and satellite cell activation in skeletal muscle

Satellite cells, the stem-like cells of skeletal muscles, are activated with various forms of exercise. The mechanisms of such activation are unknown. Exercise may activate satellite cells by increasing growth factors, specifically, hepatocyte growth factor (HGF) levels. This dissertation addressed the following questions: Do extracts made from exercised animal's muscle have increased mitogenic activity? If so, is the increased mitogenic activity due to increased HGF protein levels? Rats were assigned to either an unexercised control group (NAV), a habituated control group (HAB), or an exercise group (6HR, 12HR, 24HR). HAB and exercise groups were habituated to treadmill running. After two rest days, HAB animals were sacrificed. Exercise animals performed a 60-minute run and were sacrificed 6, 12, or 24 hours later. All animals received a 5-bromo-2-deoxyuridine (BrdU) injection 1 hour prior to sacrifice to label all activated satellite cells. In vivo satellite cell activation was examined by BrdU-labeling on isolated fiber segments. Muscle extracts (PME) were prepared and their mitogenic activity analyzed by an in vitro bioassay. HGF within PMEs from each group were analyzed by immunoblotting. NAV soleus PME inhibited myoblast proliferation compared to control medium alone. This inhibition was partially reversed with PME from 6HR and 12HR groups and fully reversed with PME from HAB and 24HR groups. HGF concentration in soleus PMEs was the same in all groups. Unlike soleus PMEs, there was no difference in the mitogenic activity of plantaris PMEs therefore HGF levels in plantaris PMEs were not analyzed. In vivo satellite cell BrdU labeling index did not change in either the soleus or plantaris following exercise. Naïve soleus muscle contains soluble factors that inhibit myoblast proliferation; however, a small amount of exercise can reverse this inhibition. In contrast to the soleus, soluble factors from naïve plantaris muscle do not inhibit myoblast proliferation. In addition, exercise does not alter plantaris extract mitogenic activity. Further work is needed to identify the mitogenic inhibitor present in naïve soleus muscle.