SAES-422 Multistate Research Act

Arizona Station. The Station demonstrated that hepatocyte growth factor (HGF) may be involved in linking mechanical perturbation of muscle to satellite cell activation. Involvement of NO in HGF release and satellite cell activation during stretch was also demonstrated, indicating that stretch triggers an intracellular cascade of events including NO synthesis, resulting in HGF release and satellite cell activation. Subsequent results indicated that calcium and calmodulin stimulate the activity of NOS, leading to the production of NO and HGF release from isolated satellite cells. The Station elucidated the functions of calpains in living cells. Inhibition of calpain activity prevented formation of integrin clusters and the ability of bovine aortic endothelial cells to spread, form focal adhesions, actin filament networks, and stress fibers, demonstrating that calpain activity is required for formation of integrin clusters. Results also indicated that 1⁄4-calpain cleaves RhoA to produce an inactive form of RhoA that inhibits stress fiber assembly. The Station in collaboration with Dr. Kathryn Wagner at Johns Hopkins used myostatin-null mice to investigate the long-term effects of myostatin blockade on muscle growth and function. Senescent myostatin null mice continued to have normal muscle with increased mass and strength relative to controls. Muscles of senescent myostatin-null mice regenerated robustly from both chronic and acute injury. Early markers of regeneration were enhanced in the absence of myostatin, suggesting a mechanism for the attenuation of dystrophic features found in mdx mice lacking myostatin.