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Evidence-Based Complementary and Alternative Medicine
Volume 2011 (2011), Article ID 395458, 12 pages
Original Article

Schwann Cell Migration Induced by Earthworm Extract via Activation of PAs and MMP2/9 Mediated through ERK1/2 and p38

1Graduate Institute of Chinese Medical Science, China Medical University, Taiwan
2School of Chinese Medicine, China Medical University, Taiwan
3Emergency Department, China Medical University Hospital, Taiwan
4Department of Neurosurgery, Chia-Yi Christian Hospital, Chia-Yi, Taiwan
5Department of Healthcare Administration, Asia University, Taiwan
6Department of Pediatrics, Medical Research and Medical Genetics, China Medical University, Taiwan
7Department of Biological Science and Technology, China Medical University, Taiwan
8School of Post-Baccalaureate Chinese Medicine, China Medical University, Taiwan
9Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan
10Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan

Received 10 February 2009; Accepted 6 August 2009

Copyright © 2011 Yung-Ming Chang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The earthworm, which has stasis removal and wound-healing functions, is a widely used Chinese herbal medicine in China. Schwann cell migration is critical for the regeneration of injured nerves. Schwann cells provide an essentially supportive activity for neuron regeneration. However, the molecular migration mechanisms induced by earthworms in Schwann cells remain unclear. Here, we investigate the roles of MAPK (ERK1/2, JNK and p38) pathways for earthworm-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in Schwann cells. Moreover, earthworm induced phosphorylation of ERK1/2 and p38, but not JNK, activate the downstream signaling expression of PAs and MMPs in a time-dependent manner. Earthworm-stimulated ERK1/2 and p38 phosphorylation was attenuated by pretreatment with U0126 and SB203580, resulting in migration and uPA-related signal pathway inhibition. The results were confirmed using small interfering ERK1/2 and p38 RNA. These results demonstrated that earthworms can stimulate Schwann cell migration and up-regulate PAs and MMP2/9 expression mediated through the MAPK pathways, ERK1/2 and p38. Taken together, our data suggests the MAPKs (ERK1/2, p38)-, PAs (uPA, tPA)-, MMP (MMP2, MMP9) signaling pathway of Schwann cells regulated by earthworms might play a major role in Schwann cell migration and nerve regeneration.