The Low-Affinity Receptor for Neurotrophins p75NTR Plays a Key Role for Satellite Cell Function in Muscle Repair Acting via RhoA

• DOI: 10.1091/mbc.e09-01-0012
• Publication Date: 2009-06-25T01:52:27Z
• Authors: Daniela Deponti; Roberta Buono; Giuseppina Catanzaro; Clara De Palma; Renato Longhi; Raffaella Meneveri; Nereo Bresolin; Maria Teresa Bassi; Giulio Cossu; Emilio Clementi; Silvia Brunelli
• Keywords: 0301 basic medicine; Satellite Cells, Skeletal Muscle; Muscle Fibers, Skeletal; Cell Differentiation; Receptors, Nerve Growth Factor; Cell Fusion; Mice; 03 medical and health sciences; Nerve Growth Factor; Animals; Cell Differentiation; Cell Fusion; Cells, Cultured; Cytoskeleton; Humans; Mice; Muscle Fibers, Skeletal; Muscle, Skeletal; Nerve Growth Factor; Receptors, Nerve Growth Factor; Regeneration; Satellite Cells, Skeletal Muscle; Signal Transduction; rhoA GTP-Binding Protein; Molecular Biology; Cell Biology; Animals; Humans; Regeneration; Muscle, Skeletal; rhoA GTP-Binding Protein; Cells, Cultured; Cytoskeleton; Signal Transduction

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 p75NTR 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.