The Growth Factor Myostatin, a Key Regulator in Skeletal Muscle Growth and Homeostasis

Abstract

Skeletal muscle possesses the ability to both respond and adapt to changing environmental stimuli, leading to a set of metabolic and morphological adaptations, which allow it to better meet the energy demands of sustained physical activity. Great progress has been achieved over the past years by means of innovative molecular techniques, which has led to the discovery of new growth factors and the identification of molecular mechanisms involved in the regulation of muscle development. These findings provide new starting points to understand the molecular mechanisms involved in the adaptation of skeletal muscle to exercise training. One of these new identified growth factors is myostatin, a member of the transforming growth factor-beta family of proteins that has been demonstrated to play a fundamental role in the regulation of skeletal muscle growth during embryogenesis. Blocking of the myostatin signalling transduction pathway by specific inhibitors and genetic manipulations has been shown to result in a dramatic increase of skeletal muscle mass. This review focuses on the importance of myostatin in mediating skeletal muscle homeostasis in response to training as well as during the progress of myogenic disease, like atrophy or dystrophy. Manipulations of myostatin signalling may be useful for agriculture applications, treatment of muscle diseases, inhibition of muscle atrophy and last but not least as life style drugs in antiaging therapies or manipulations of the muscle to fat ratio. Drugs with the ability to modulate myostatin signalling may have the potential to enhance physical performance in athletes and therefore they probably represent a new class of doping substances.

Effects of streptozotocin-induced diabetes and physical training on gene expression of titin-based stretch-sensing complexes in mouse striated muscle

“…Lack of myostatin partially suppresses both fat accumulation and the development of hyperglycemia in mouse models of obesity and type 2 diabetes (A y , Lep ob/ob ) (42). Endurance training decreases myostatin mRNA content in fast (gastrocnemius, vastus lateralis) but not in slow (soleus) skeletal muscles (36). In muscle atrophies induced by glucocorticoids or muscle unloading, myostatin expression is increased (36).…”

“…Endurance training decreases myostatin mRNA content in fast (gastrocnemius, vastus lateralis) but not in slow (soleus) skeletal muscles (36). In muscle atrophies induced by glucocorticoids or muscle unloading, myostatin expression is increased (36).…”

“…The ability to increase muscle mass and the rate of protein synthesis depend on the severity of the disease (10,11). Gene expressions of MLP and MARPs are known to increase and that of myostatin to decrease after physical activity (2,36). However, the effects of training on titin stretch-sensing complexes are not well known.…”

Placental expression of myostatin and follistatin-like-3 protein in a model of developmental programming

“…Further studies have identified this action to occur through proteolytic cleavage of the myostatin precursor protein (52 kDa) that is proteolytically cleaved twice to release the biologically mature form of myostatin (ϳ12 kDa) (19,20,25). Both the unprocessed and mature forms of myostatin are capable of forming disulfide-linked dimers.…”

Terapia gênica, doping genético e esporte: fundamentação e implicações para o futuro

“…Its action consists in regulating the proliferation of the myoblasts during the embrionary period as well as the protein synthesis in the skeletal muscles during and after the embrionary period (36)(37)(38)(39) . In some cattle breeds it is observed the uncommon growth of muscles of some animals (a phenomenon known as double muscling).…”