title: The Neuregulin1/ErbB system is selectively regulated during peripheral nerve degeneration and regeneration.
abstract: The peripheral nervous system has an intrinsic capability to regenerate, crucially related to the ability of Schwann cells (SC) to create a permissive environment, for example, through production of regeneration-promoting neurotrophic factors. Survival, proliferation, migration and differentiation of SC into a myelinating phenotype during development and after injury is regulated by different Neuregulin1 (NRG1) isoforms. This study investigates the expression of different NRG1 isoforms and of their ErbB receptors in distal rat median nerve samples under regenerating conditions after a mild (crush) and more severe (end-to-end repair) injury and under degenerating condition. The expression of the NRG1/ErbB system was evaluated at mRNA and protein level, and demonstrated to be specific for distinct and consecutive phases following nerve injury and regeneration or the progress in degeneration. For the first time a detailed analysis of expression profiles not only of soluble and transmembrane NRG1 isoforms, but also of alpha and beta as well as type a, b and c isoforms is presented. The results of mRNA and protein expression pattern analyses were related to nerve ultrastructure changes evaluated by electron microscopy. In particular, transmembrane NRG1 isoforms are differentially regulated and proteolytically processed under regeneration and degeneration conditions. Soluble NRG1 isoforms alpha and beta, as well as type a and b, are strongly upregulated during axonal regrowth, while type c NRG1 isoform is downregulated. This is accompanied by an upregulation of ErbB receptors. This accurate regulation suggests that each molecule plays a specific role that could be clinically exploited to improve nerve regeneration.
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Regione Gonzole 10, Orbassano, 10043, Italy.|Neuroscience Institute of the 'Cavalieri Ottolenghi' Foundation (NICO), University of Torino, Orbassano, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ronchi
authors.affiliation: Hannover Medical School, Institute of Neuroanatomy, Hannover, Germany.|Center for Systems Neuroscience (ZSN), Hannover, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Haastert-Talini
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Regione Gonzole 10, Orbassano, 10043, Italy.
authors.forename: Benedetta Elena
authors.initials: BE
authors.lastname: Fornasari
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Regione Gonzole 10, Orbassano, 10043, Italy.|Neuroscience Institute of Torino (NIT), University of Torino, Orbassano, Italy.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perroteau
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Regione Gonzole 10, Orbassano, 10043, Italy.|Neuroscience Institute of the 'Cavalieri Ottolenghi' Foundation (NICO), University of Torino, Orbassano, Italy.|Neuroscience Institute of Torino (NIT), University of Torino, Orbassano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Geuna
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Regione Gonzole 10, Orbassano, 10043, Italy.|Neuroscience Institute of Torino (NIT), University of Torino, Orbassano, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Gambarotta
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D009416:Nerve Regeneration; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D020033:Protein Isoforms; D012333:RNA, Messenger; D066246:ErbB Receptors
keywords: NRG1/ErbB; biomolecular analysis; electron microscopy; nerve injury; remyelination