Neuregulin1 (NRG1) and its receptors (ErbBs) play a key role in the biomolecular mechanisms implicated in post-traumatic recovery of the neuromuscular function. The aim of this study was to investigate the changes in NRG1 and ErbB receptors expression after nerve reconstruction by means of bioengineered tissue scaffolds (muscle-vein combined tubes) used to bridge nerve lesions with substance loss. Surgery was carried out in adult female rats. The left median nerve was transected and repaired by means of muscle-vein combined conduits. Repaired nerves and reinnervated muscles were withdrawn at 5-15-30 days postoperative and processed for immunohistochemistry and RT-PCR analysis. Results of the analysis of nerve samples showed an early and progressive increase in the expression of NRG1-alpha isoform while the appearance of the beta isoform was delayed. As regards ErbB2 and ErbB3 receptors, their expression increased progressively along the bioengineered scaffolds, though with different kinetics. Results of the analysis of muscle samples, showed a rapid and significant up-regulation of NRG1-alpha only. As regards ErbBs receptors, we observed the up-regulation of ErbB2, ErbB3 and ErbB4-cyt1 after denervation and their consequent down-regulation when axons reinnervate the muscle. Taken together, our results showed that variations of the NRG1/ErbB system activation play a key role in transected peripheral nerves as well as in denervated skeletal muscles. While the mechanisms through which the NRG1/ErbB system is regulated are still partially unknown, our data suggest that the existence of NRG1’s autocrine and paracrine trophic loops shared by both glial and muscle cells can be at the basis of the effectiveness of muscle-vein-combined scaffolds for repairing nerve defects. Financial support from MIUR (FIRB RBAU01BJ95) and Regione Piemonte (Prog. Ric. San. Fin. 2004, Prog DIADI “Tesina” 2003-2006).
Variations in Neuregulin-1 and ErbB receptors expression in neuromuscular recovery after nerve reconstruction by means of bioengineered tissue scaffolds
NICOLINO, SILVIA;RAIMONDO, Stefania;TOS, PIERLUIGI;GAMBAROTTA, Giovanna;GEUNA, Stefano;PERROTEAU, Isabelle
2006-01-01
Abstract
Neuregulin1 (NRG1) and its receptors (ErbBs) play a key role in the biomolecular mechanisms implicated in post-traumatic recovery of the neuromuscular function. The aim of this study was to investigate the changes in NRG1 and ErbB receptors expression after nerve reconstruction by means of bioengineered tissue scaffolds (muscle-vein combined tubes) used to bridge nerve lesions with substance loss. Surgery was carried out in adult female rats. The left median nerve was transected and repaired by means of muscle-vein combined conduits. Repaired nerves and reinnervated muscles were withdrawn at 5-15-30 days postoperative and processed for immunohistochemistry and RT-PCR analysis. Results of the analysis of nerve samples showed an early and progressive increase in the expression of NRG1-alpha isoform while the appearance of the beta isoform was delayed. As regards ErbB2 and ErbB3 receptors, their expression increased progressively along the bioengineered scaffolds, though with different kinetics. Results of the analysis of muscle samples, showed a rapid and significant up-regulation of NRG1-alpha only. As regards ErbBs receptors, we observed the up-regulation of ErbB2, ErbB3 and ErbB4-cyt1 after denervation and their consequent down-regulation when axons reinnervate the muscle. Taken together, our results showed that variations of the NRG1/ErbB system activation play a key role in transected peripheral nerves as well as in denervated skeletal muscles. While the mechanisms through which the NRG1/ErbB system is regulated are still partially unknown, our data suggest that the existence of NRG1’s autocrine and paracrine trophic loops shared by both glial and muscle cells can be at the basis of the effectiveness of muscle-vein-combined scaffolds for repairing nerve defects. Financial support from MIUR (FIRB RBAU01BJ95) and Regione Piemonte (Prog. Ric. San. Fin. 2004, Prog DIADI “Tesina” 2003-2006).
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