Myostatin: a negative regulator of muscle development and maintenance

Abstract

International audienceMyostatin is a member of the TGF beta family which plays a major role in negative regulation of muscle development. Not only do mstn-/-mice display a dramatic increase in skeletal muscle mass, cattle harboring loss of function mutations in the myostatin gene also exhibit muscle overdevelopment associated to a shift in the contractile and metabolic features of muscles fibers. The occurrence of such mutations associated to increased muscle mass in humans has also been reported. Recent data clearly suggest that myostatin is also involved in muscle tissue maintenance in adults, in particular by activating pathways leading to proteolysis and satellite cell activity. As myostatin expression generally increases during muscle atrophy, some promising attempts have been made to improve the behavior of some muscle pathologies, such as myopathies, by targeting myostatin activity. These attempts have opened the way for novel pharmacological strategies focused on skeletal muscle diseases. Here we review the physiopathological consequences of changes in myostatin expression and their clinical interest. We also briefly address the myostatin molecular pathway by describing the knowledge which makes it possible to test the efficiency of pharmacological inhibition of this growth factor activity in muscle pathologies