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Denervation and reinnervation of adult skeletal muscle modulate mRNA expression of neuregulin‐1 and ErbB receptors
Author(s) -
Nicolino Silvia,
Panetto Arianna,
Raimondo Stefania,
Gambarotta Giovanna,
Guzzini Matteo,
Fornaro Michele,
Battiston Bruno,
Tos Perluigi,
Geuna Stefano,
Perroteau Isabelle
Publication year - 2009
Publication title -
microsurgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.031
H-Index - 63
eISSN - 1098-2752
pISSN - 0738-1085
DOI - 10.1002/micr.20636
Subject(s) - reinnervation , medicine , denervation , neuregulin 1 , neuregulin , receptor , erbb , skeletal muscle , messenger rna , neuroscience , anatomy , endocrinology , gene , biology , biochemistry
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 α‐, but not β‐, 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 α‐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 α‐NRG1‐mediated gliotrophic loop in denervated Schwann cells provides a possible explanation for the effectiveness of muscle conduits for tubulization nerve repair. © 2009 Wiley‐Liss, Inc. Microsurgery, 2009.