Originally published In Press as doi:10.1074/mcp.M800076-MCP200 on May 14, 2008.
Molecular & Cellular Proteomics 7:1668-1687, 2008.
© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
Research
Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach*,S
Ming-Chu Tsai ,
Li-Fen Shen ,
Huai-Sheng Kuo ,
Henrich Cheng ,¶,|| and
Kin-Fu Chak ,**
From the Institute of Biochemistry and Molecular Biology, School of Life Sciences and || Institute of Pharmacology and Department of Surgery, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan and Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute and ¶ Center for Neural Regeneration, Taipei Veterans General Hospital, Taipei 11217, Taiwan
Acidic fibroblast growth factor (aFGF; also known as FGF-1) is a potent neurotrophic factor that affects neuronal survival in the injured spinal cord. However, the pathological changes that occur with spinal cord injury (SCI) and the attribution to aFGF of a neuroprotective effect during SCI are still elusive. In this study, we demonstrated that rat SCI, when treated with aFGF, showed significant functional recovery as indicated by the Basso, Beattie, and Bresnahan locomotor rating scale and the combined behavior score (p < 0.01–0.001). Furthermore proteomics and bioinformatics approaches were adapted to investigate changes in the global protein profile of the damaged spinal cord tissue when experimental rats were treated either with or without aFGF at 24 h after injury. We found that 51 protein spots, resolvable by two-dimensional PAGE, had significant differential expression. Using hierarchical clustering analysis, these proteins were categorized into five major expression patterns. Noticeably proteins involved in the process of secondary injury, such as astrocyte activation (glial fibrillary acidic protein), inflammation (S100B), and scar formation (keratan sulfate proteoglycan lumican), which lead to the blocking of injured spinal cord regeneration, were down-regulated in the contusive spinal cord after treatment with aFGF. We propose that aFGF might initiate a series of biological processes to prevent or attenuate secondary injury and that this, in turn, leads to an improvement in functional recovery. Moreover the quantitative expression level of these proteins was verified by quantitative real time PCR. Furthermore we identified various potential neuroprotective protein factors that are induced by aFGF and may be involved in the spinal cord repair processes of SCI rats. Thus, our results could have a remarkable impact on clinical developments in the area of spinal cord injury therapy.
** To whom correspondence should be addressed: Inst. of Biochemistry and Molecular Biology, National Yang-Ming University, School of Life Sciences, 155 Li Nong St., Section 2, Taipei 11221, Taiwan. Tel.: 886-2-28267129; Fax: 886-2-28264843; E-mail: kfchak{at}ym.edu.tw

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Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.
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