RGD Reference Report - Denervation and reinnervation of adult skeletal muscle modulate mRNA expression of neuregulin-1 and ErbB receptors. - Rat Genome Database

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Denervation and reinnervation of adult skeletal muscle modulate mRNA expression of neuregulin-1 and ErbB receptors.

Authors: Nicolino, S  Panetto, A  Raimondo, S  Gambarotta, G  Guzzini, M  Fornaro, M  Battiston, B  Tos, P  Geuna, S  Perroteau, I 
Citation: Nicolino S, etal., Microsurgery. 2009;29(6):464-72. doi: 10.1002/micr.20636.
RGD ID: 10449020
Pubmed: PMID:19296522   (View Abstract at PubMed)
DOI: DOI:10.1002/micr.20636   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Erbb2  (erb-b2 receptor tyrosine kinase 2)
Erbb3  (erb-b2 receptor tyrosine kinase 3)
Erbb4  (erb-b2 receptor tyrosine kinase 4)
Nrg1  (neuregulin 1)

Genes (Mus musculus)
Erbb2  (erb-b2 receptor tyrosine kinase 2)
Erbb3  (erb-b2 receptor tyrosine kinase 3)
Erbb4  (erb-b2 receptor tyrosine kinase 4)
Nrg1  (neuregulin 1)

Genes (Homo sapiens)
ERBB2  (erb-b2 receptor tyrosine kinase 2)
ERBB3  (erb-b2 receptor tyrosine kinase 3)
ERBB4  (erb-b2 receptor tyrosine kinase 4)
NRG1  (neuregulin 1)


Additional Information