The myostatin gene: physiology and pharmacological relevance
ABSTRACT 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.
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ABSTRACT: Muscle stem cell (satellite cell) activation post muscle injury is a transient and critical step in muscle regeneration. It is regulated by physiological cues, signaling molecules, and epigenetic regulatory factors. The mechanisms that coherently turn on the complex activation process shortly after trauma are just beginning to be illuminated. In this review, we will discuss the current knowledge of satellite cell activation regulation.Cellular and Molecular Life Sciences CMLS 01/2015; DOI:10.1007/s00018-014-1819-5 · 5.86 Impact Factor
- Annals of Neurology 01/2010; 67(1):148. DOI:10.1002/ana.21663 · 11.91 Impact Factor