ERK1/2-Mediated Schwann Cell Proliferation in the Regenerating Sciatic Nerve by Treadmill Training

作者：Seo Tae Beom; Oh Myung Jin; You Byoung Gun; Kwon Ku Birm; Chang In Ae; Yoon Jin Hwan; Lee Chan Yong; Namgung Uk^*

来源：Journal of Neurotrauma, 2009, 26(10): 1733-1744.

DOI：10.1089/neu.2008.0711

• c-Jun
• ERK1/2
• regeneration
• Schwann cell
• sciatic nerve
• treadmill training

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.

• 出版日期2009-10