Journal
MICROSURGERY
Volume 29, Issue 6, Pages 464-472Publisher
WILEY
DOI: 10.1002/micr.20636
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Funding
- Regione Piemonte
- The Ministero Italiano dell'Universita e delta Ricerca (MIUR)
- FIRB [RBAU01BJ95]
- PRIN [2005057088]
- The Univesity of Turin
- Compagnia di Sa Paolo
- The Regione Piemonte
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Skeletal muscle atrophy represents one of the main causes of poor outcome of microsurgical nerve reconstruction. Recent studies have pointed to the importance of the neuregulin/ErbB signaling pathway in the development and regeneration of the neuromuscular system. Here, we show by immunohistochemistry, RT-PCR, and Western blotting analyses, in an in vivo model of adult skeletal muscle denervation/reinnervation, that expression of Neuregulin1 (NRG1) and ErbB receptors is regulated by the innervation condition. We found out that a significant upregulation of the alpha-, but not beta-, isoform of NRG1, as well as of ErbB2, ErbB3, and ErbB4-cyt1 isoform occurs as a consequence of denervation of flexor digitorum muscles of the rat forelimb by median nerve transection. Moreover, after tubulization median nerve repair, and consequent muscle reinnervation, all messengers of the NRG1/ErbB system are promptly downregulated. Therefore, our results suggest the existence of a alpha-NRG1-mediated autocrine and/or paracrine trophic loop in skeletal muscles that is activated after denervation and promptly deactivated after nerve reconstruction. This myotrophic loop is a promising therapeutic target for the prevention of muscle atrophy. Yet, the recent demonstration of a similar alpha-NRG1-mediated gliotrophic loop in denervated Schwann cells provides a possible explanation for the effectiveness of muscle conduits for tubulization nerve repair. (C) 2009 Wiley-Liss, Inc. Microsurgery 29:464-472, 2009.
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