The myostatin gene: physiology and pharmacological relevance.
Myostatin, which was cloned in 1997, is a potent inhibitor of skeletal muscle growth and member of the tumour growth factor-beta family. Disruption of the myostatin gene in mice induces a dramatic increase in muscle mass, caused by a combination of hypertrophy and hyperplasia. Natural mutations occurring in cattle were also associated with a significant increase in muscle mass and, recently, an inactivating myostatin mutation associated with the same phenotype was identified in humans. Studies into the molecular basis of this antimyogenic influence led to the conclusion that myostatin inhibits myoblast proliferation and differentiation through a classical tumour growth factor-beta pathway involving the activin receptor ActRIIB and Smads 2 and 3. Approaches that induce myostatin depletion or inactivation have led to a significant improvement in muscle regeneration processes, especially in degenerative diseases, through stimulation of satellite cell proliferation and differentiation. These promising data open the way to new therapeutic approaches in muscle diseases through targeting of the myostatin pathway.
Joulia-Ekaza
Dominique
D
UFR Sciences de la Nature, Laboratoire de Physiologie Animale et Pharmacologie, Université d'Abobo-Adjamé, Abidjan, Côte d'Ivoire.
Cabello
Gérard
G
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D009133:Muscular Atrophy / Q000378:metabolism; D055435:Myostatin; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta