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eCAM Advance Access published online on October 6, 2009
eCAM, doi:10.1093/ecam/nep131
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© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

Yung-Ming Chang1,2, Ying-Ting Shih1, Yueh-Sheng Chen1, Chien-Liang Liu3, Wen-Kuei Fang4, Chang-Hai Tsai5, Fuu-Jen Tsai1,6, Wei-Wen Kuo7,*, Tung-Yuan Lai8,* and Chih-Yang Huang1,9,10,*

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

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.

Keywords: earthworm – migration – peripheral nerve regeneration – Schwann cells

For reprints and all correspondence: Chih-Yang Huang, PhD, Graduate Institute of Chinese Medical Science and Institute of Basic Medical Science, China Medical University, No. 91, Hsueh-Shih Road, Taichung, 404, Taiwan. Tel: +886-4-2205-3366, ext. 3313; Fax: +886-4-2207-0465; E-mail: cyhuang{at}mail.cmu.edu.tw

*These authors contribute equally to this work.

Received February 10, 2009; accepted August 6, 2009


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