title: Neuregulin facilitates nerve regeneration by speeding Schwann cell migration via ErbB2/3-dependent FAK pathway.
abstract: BACKGROUND
  Adequate migration of Schwann cells (Sc) is crucial for axon-guidance in the regenerative process after peripheral nerve injury (PNI). Considering neuregulin-erbB-FAK signaling is an essential pathway participating in the regulation of Sc migration during development, the present study is aimed to examine whether neuregulin would exert its beneficial effects on adult following PNI and further determine the potential changes of downstream pathway engaged in neuro-regeneration by both in vitro and in vivo approaches.
  
  
  RESULTS
  Cultured RSC96 cells treated with neuregulin were processed for erbB2/3 immunofluorescence and FAK immunoblotings. The potential effects of neuregulin on Sc were assessed by cell adherence, spreading, and migration assays. In order to evaluate the functional significance of neuregulin on neuro-regeneration, the in vivo model of PNI was performed by chronic end-to-side neurorrhaphy (ESN). In vitro studies indicated that after neuregulin incubation, erbB2/3 were not only expressed in cell membranes, but also distributed throughout the cytoplasm and nucleus of RSC96 cells. Activation of erbB2/3 was positively correlated with FAK phosphorylation. Neuregulin also increases Sc adherence, spreading, and migration by 127.2 ± 5.0%, 336.8 ± 3.0%, and 80.0 ± 5.7%, respectively. As for in vivo study, neuregulin significantly accelerates the speed of Sc migration and increases Sc expression in the distal stump of injured nerves. Retrograde labeling and compound muscle action potential recordings (CMAP) also showed that neuregulin successfully facilitates nerve regeneration by eliciting noticeably larger CMAP and promoting quick re-innervation of target muscles.
  
  
  CONCLUSIONS
  As neuregulin successfully improves axo-glial interaction by speeding Sc migration via the erbB2/3-FAK pathway, therapeutic use of neuregulin may thus serve as a promising strategy to facilitate the progress of nerve regeneration after PNI.
authors.affiliation: Department of Anatomy, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Chang
authors.forename: Ming-Kwang
authors.initials: MK
authors.lastname: Shyu
authors.forename: Guo-Fang
authors.initials: GF
authors.lastname: Tseng
authors.forename: Chiung-Hui
authors.initials: CH
authors.lastname: Liu
authors.forename: Hung-Shuo
authors.initials: HS
authors.lastname: Chang
authors.forename: Chyn-Tair
authors.initials: CT
authors.lastname: Lan
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Hsu
authors.forename: Wen-Chieh
authors.initials: WC
authors.lastname: Liao
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D004594:Electrophysiology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D015233:Models, Statistical; D009416:Nerve Regeneration / Q000502:physiology*; D020890:Neuregulin-1 / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D012038:Regeneration; D012583:Schwann Cells / Q000166:cytology*; D015398:Signal Transduction
chemical_list: D051417:Focal Adhesion Kinase 1; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C483804:Erbb2 protein, rat; C496052:Ptk2 protein, rat