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Skeletal muscle healing after injury can be divided into three distinct but overlapping phases. The destruction phase is characterized by rupture followed by necrosis of muscle fibers, formation of hematoma and inflammatory reaction. During the repair phase a necrotic tissue is phagocyted by macrophages, muscle fibers are regenerating and connective tissue scars are formed. The remodeling phase concerns the period when regenerating muscle fibers mature, scar contraction and reorganization occurs and the muscle recovers its functional efficiency. Proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and growth factors (FGF, IGF, TGF-β, HGF) play a critical role in all phases of muscle repair. Moreover, chemokines expressed at early stages of myogenesis can regulate the survival and proliferation of myoblasts. Chemokines expressed in vivo in muscle cells can directly influence myogenesis, but can also act in a paracrine manner by recruiting the immune cells (macrophages) to injured skeletal muscles, which is crucial for the regeneration process. Identification of molecules regulating myogenesis, like cytokines, chemokines and growth factors, contributes to the exploration of molecular mechanisms that can improve muscle regeneration after injury, diseases, surgery and increase the effectiveness of cell transplantation.
The article describes the principles of the insulin signaling pathway and the latest research results indicating the new role of insulin in modulating mitochondrial activity during muscle development. Myogenesis is considered to be an extensive energy-demanding process where mitochondria are the main source of ATP. Moreover, a number of reports emphasize that insulin is the most likely factor regulating prenatal muscle growth. Despite the fact that research into the affect of insulin onto myogenesis is incomplete, the role of mitochondria in muscle formation is thought to be essential in order to comprehend both whole-body growth and development. Insulin stimulates the expression of mitochondrial proteins in muscle cells whereas the activity of some targets of the insulin signaling pathway depends on ATP supply (e. g. mTOR). Similarly, alterations in available energy supply, resulting from the impaired function of mitochondria affect the cells sensitivity to insulin as well as leading to myopaties in the developing muscle tissue.
Postnatal growth and regeneration capacity of skeletal muscles is dependent mainly on adult muscle stem cells called satellite cells. Satellite cells are quiescent mononucleated cells that are normally located outside the sarcolemma within the basal lamina of the muscle fiber. Their activation, which results from injury, is manifested by mobilization, proliferation, differentiation and, ultimately, fusion into new muscle fibers. The satellite cell pool is responsible for the remarkable regenerative capacity of skeletal muscles. Moreover, these cells are capable of self-renewal and can give rise to myogenic progeny.
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