Redox remodeling: a candidate regulator of HMGB1 function in injured skeletal muscle.
High-mobility group box-1 (HMGB1) is a prototypical endogenous signal that links tissue necrosis and wound healing. Extracellular HMGB1 has apparently contrasting biological actions: it sustains inflammation (with the possible establishment of autoimmunity or of self-maintaining tissue damage) while activating and recruiting stem cells, which foster tissue repair. However, little is known about the role environmental cues play in the extracellular functions of HMGB1. The skeletal muscle is an optimal tissue model to help us unravel these underlying molecular events. Here, sterile injury triggers a potent inflammatory response that includes infiltration by inflammatory leukocytes and the parallel activation, proliferation, and fusion of muscle-specific stem cells. Recent data suggest that the regulation of environmental redox is critical for the bioactivity of HMGB1, which is extremely sensitive to oxidation. Moreover, data suggest a potential role for infiltrating alternatively activated macrophages to influence the outcome of inflammatory responses to sterile skeletal muscle necrosis.
Vezzoli
Michela
M
Innate Immunity and Tissue Remodeling Unit, San Raffaele Scientific Institute, Milano, Italy.
Castellani
Patrizia
P
Campana
Lara
L
Corna
Gianfranca
G
Bosurgi
Lidia
L
Manfredi
Angelo A
AA
Bianchi
Marco E
ME
Rubartelli
Anna
A
Rovere-Querini
Patrizia
P
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D024243:HMGB1 Protein / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000166:cytology; D018482:Muscle, Skeletal / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology
D017931:DNA Primers; D024243:HMGB1 Protein; D017382:Reactive Oxygen Species