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Serum Proteomic Analysis of Extracorporeal Shock Wave Therapy–Enhanced Diabetic Wound Healing in a Streptozotocin-Induced Diabetes Model

Yang, Ming-Yu Ph.D.; Chiang, Yuan-Cheng M.D.; Huang, Yu-Ting M.S.; Chen, Chien-Chang M.D.; Wang, Feng-Sheng Ph.D.; Wang, Ching-Jen M.D.; Kuo, Yur-Ren M.D., Ph.D.

Plastic and Reconstructive Surgery: January 2014 - Volume 133 - Issue 1 - p 59–68
doi: 10.1097/
Experimental: Original Articles

Background: Previous studies have demonstrated that extracorporeal shock wave therapy has a significant positive effect on accelerating diabetic wound healing. However, the systemic effect after therapy is still unclear.

Methods: This study investigated the plasma protein expression in the extracorporeal shock wave therapy group and diabetic controls using proteomic study. A dorsal skin defect (6 × 5 cm) in a streptozotocin-induced diabetic Wistar rat model was used. Diabetic rats receiving either no therapy or extracorporeal shock wave therapy after wounding were analyzed. The spots of interest were subjected to in-gel trypsin digestion and matrix-assisted laser desorption ionization time-of-flight mass spectrometry to elucidate the peptide mass fingerprints. The mass spectrometric characteristics of the identified proteins, including their theoretical isoelectric points, molecular weights, sequence coverage, and Mascot score, were analyzed. Protein expression was validated using immunohistochemical analysis of topical periwounding tissues.

Results: The proteomic study revealed that at days 3 and 10 after therapy rats had significantly higher abundance of haptoglobin and significantly lower levels of the vitamin D-binding protein precursor as compared with the diabetic controls. Immunohistochemical staining of topical periwounding tissue also revealed significant upregulation of haptoglobin and downregulation of vitamin D-binding protein expression in the extracorporeal shock wave therapy group, which was consistent with the systemic proteome study.

Conclusion: Proteome analyses demonstrated an upregulation of haptoglobin and a downregulation of vitamin D-binding protein in extracorporeal shock wave therapy–enhanced diabetic wound healing.

Tao-Yuan and Kaohsiung, Taiwan

From the Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University; and the Department of Plastic and Reconstructive Surgery, Medical Research, and the Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine.

The first two authors contributed equally to this work and should be considered co-first authors.

Received for publication March 28, 2013; accepted June 13, 2013.

Disclosure: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this article.

Yur-Ren Kuo, M.D., Ph.D., Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 83301, Taiwan,,

©2014American Society of Plastic Surgeons