title: ERK1/2-mediated Schwann cell proliferation in the regenerating sciatic nerve by treadmill training.
abstract: Proliferation of Schwann cells in the injured peripheral nerve supports axonal regeneration, and physical training in experimental animals has been shown to promote nerve regeneration. Extracellular signal-regulated kinase 1/2 (ERK1/2) activity can mediate neuronal responses to lesion signals, but its role in non-neuronal cells in the injured area is largely unknown. Here we report that treadmill training (TMT) facilitates axonal regeneration via the upregulation of phospho-ERK1/2 protein levels in Schwann cells in the injured sciatic nerve. Low-intensity, but not high-intensity, TMT increased neurite outgrowth of dorsal root ganglion (DRG) sensory neurons and potentiated Schwann cell proliferation. TMT elevated levels of GAP-43 mRNA and protein, and phospho-ERK1/2 protein in the injured sciatic nerves. TMT also enhanced phospho-c-Jun protein levels in the injured nerve. In-vivo administration of the ERK1/2 inhibitor PD98059 eliminated phospho-c-Jun, suggesting ERK1/2 phosphorylation of the c-Jun protein. PD98059 treatment decreased levels of BrdU-labeled proliferating Schwann cells in the distal portion of the injured nerve, and delayed the axonal regrowth that was promoted by TMT. The present data suggest that increased ERK1/2 activity in Schwann cells may play an important role in TMT-mediated enhancement of axonal regeneration in the injured peripheral nerve.
authors.affiliation: Department of Oriental Medicine, Daejeon University, Daejeon, Korea.
authors.forename: Tae Beom
authors.initials: TB
authors.lastname: Seo
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Oh
authors.forename: Byoung-Gun
authors.initials: BG
authors.lastname: You
authors.forename: Ku-Birm
authors.initials: KB
authors.lastname: Kwon
authors.forename: In-Ae
authors.initials: IA
authors.lastname: Chang
authors.forename: Jin-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Chan-Yong
authors.initials: CY
authors.lastname: Lee
authors.forename: Uk
authors.initials: U
authors.lastname: Namgung
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003714:Denervation; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005080:Exercise Test; D005081:Exercise Therapy / Q000379:methods*; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D010805:Physical Conditioning, Animal / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000201:enzymology*; D012584:Sciatic Nerve / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000201:enzymology* / Q000503:physiopathology / Q000534:rehabilitation*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D019922:GAP-43 Protein; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D048052:Mitogen-Activated Protein Kinase 3