Hepatocyte growth factor affects satellite cell activation and differentiation in regenerating skeletal muscle

Hepatocyte growth factor (HGF) is the onlyknown growth factor that activates quiescent satellite cells inskeletal muscle. We hypothesized that local delivery of HGF may enhanceregeneration after trauma by increasing the number of myoblastsavailable for restoring normal tissue architecture. Injection of HGFinto muscle at the time of injury increases myoblast number but doesnot enhance tissue repair as determined using quantitative histologicalanalyses. Rather, depending on the dose and the timing of HGFadministration relative to the injury, regeneration can be inhibited.The greatest inhibitory effect is observed when HGF is administered onthe day of injury and continued for 3 days, corresponding to the time when satellite cell activation, proliferation, and earlydifferentiation normally occur. To establish a mechanism for thisinhibition, we show that HGF can act directly on primary muscle cellsto block differentiation. These results demonstrate that1) exogenous HGF synergizes withfactors in damaged muscle to increase myoblast number,2) regeneration is not regulatedsolely by myoblast number, and 3)HGF inhibits muscle differentiation both in vitro and in vivo.