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Vol. 20, Issue 16, 3620-3627, August 15, 2009

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The Low-Affinity Receptor for Neurotrophins p75^NTR Plays a Key Role for Satellite Cell Function in Muscle Repair Acting via RhoA

Daniela Deponti^*, Roberta Buono, Giuseppina Catanzaro, Clara De Palma, Renato Longhi, Raffaella Meneveri^||, Nereo Bresolin^*,¶, Maria Teresa Bassi^*, Giulio Cossu^,#, Emilio Clementi^*,, and Silvia Brunelli^,||

*E. Medea Scientific Institute, 23842 Bosisio Parini, Italy; Division of Regenerative Medicine, San Raffaele Scientific Institute, 20132 Milan, Italy; Department of Preclinical Sciences, LITA-Vialba, University of Milano, 20157 Milan, Italy; Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, ^||Department of Experimental Medicine, University of Milano-Bicocca, 20052 Monza, Italy; ^¶Department of Neurological Sciences, University of Milano, 20129 Milan, Italy; and ^#Department of Biology, University of Milano, 20130 Milan, Italy

Submitted January 7, 2009; Accepted June 15, 2009
Monitoring Editor: Marianne Bronner-Fraser

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.

Address correspondence to: Emilio Clementi (emilio.clementi{at}unimi.it) or Silvia Brunelli (brunelli.silvia{at}hsr.it)

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