Nitric oxide and repair of skeletal muscle injury.
The muscle wound healing occurs in three overlapping phases: (1) degeneration and inflammation, (2) muscle regeneration, and (3) fibrosis. Simultaneously to injury cellular infiltration by neutrophils and macrophages occur, as well as cellular 'respiratory burst' via activation of the enzyme NADPH oxidase. When skeletal muscle is stretched or injured, myogenic satellite cells are activated to enter the cell cycle, divide, differentiate and fuse with muscle fibers to repair damaged regions and to enhance hypertrophy of muscle fibers. This process depends on nitric oxide (NO) production, metalloproteinase (MMP) activation and release of hepatocyte growth factor (HGF) from the extracellular matrix. Generation of a fibrotic scar tissue, with partial loss of function, can also occur, and seems to be dependent, at least in part, on local TGF-beta expression, which can be downregulated by NO. Hence, regeneration the muscle depends on the type and severity of the injury, the appropriate inflammatory response and on the balance of the processes of remodeling and fibrosis. It appears that in all these phases NO exerts a significant role. Better comprehension of this role, as well as of the participation of other important mediators, may lead to development of new treatment strategies trying to tip the balance in favor of greater regeneration over fibrosis, resulting in better functional recovery.
Filippin
Lidiane Isabel
LI
Post-Graduation Medical Sciences Program, Medical School/Universidade Federal do Rio Grande do Sul (UFRGS), Brazil.
Moreira
Andrea Janz
AJ
Marroni
Norma Possa
NP
Xavier
Ricardo Machado
RM
D000818:Animals; D005355:Fibrosis; D006801:Humans; D018482:Muscle, Skeletal / Q000293:injuries* / Q000502:physiology / Q000648:ultrastructure; D009569:Nitric Oxide / Q000502:physiology*; D014945:Wound Healing
D009569:Nitric Oxide