The low-affinity receptor for neurotrophins p75NTR plays a key role for satellite cell function in muscle repair acting via RhoA.
Regeneration of muscle fibers, lost during pathological muscle degeneration or after injuries, is mediated by the production of new myofibres. This process, sustained by the resident stem cells of the muscle, the satellite cells, is finely regulated by local cues, in particular by cytokines and growth factors. Evidence in the literature suggests that nerve growth factor (NGF) is involved in muscle fiber regeneration; however, its role and mechanism of action were unclear. We have investigated this issue in in vivo mouse models of muscle regeneration and in primary myogenic cells. Our results demonstrate that NGF acts through its low-affinity receptor p75(NTR) in a developmentally regulated signaling pathway necessary to myogenic differentiation and muscle repair in vivo. We also demonstrate that this action of NGF is mediated by the down-regulation of RhoA-GTP signaling in myogenic cells.
Deponti
Daniela
D
E. Medea Scientific Institute, Bosisio Parini, Italy.
Buono
Roberta
R
Catanzaro
Giuseppina
G
De Palma
Clara
C
Longhi
Renato
R
Meneveri
Raffaella
R
Bresolin
Nereo
N
Bassi
Maria Teresa
MT
Cossu
Giulio
G
Clementi
Emilio
E
Brunelli
Silvia
S
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002459:Cell Fusion; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000502:physiology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000473:pathology / Q000502:physiology*; D020932:Nerve Growth Factor / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D020932:Nerve Growth Factor; D020742:rhoA GTP-Binding Protein