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https://hdl.handle.net/2440/23346
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Type: | Journal article |
Title: | Mitogenic bovine whey extract modulates matrix metalloproteinase-2,-9, and tissue inhibitor of matrix metalloproteinase-2 levels in chronic leg ulcers |
Author: | Varelias, A. Cowin, A. Adams, D. Harries, R. Cooter, R. Belford, D. Fitridge, R. Rayner, T. |
Citation: | Wound Repair and Regeneration, 2006; 14(1):28-37 |
Publisher: | Blackwell Publishing Inc |
Issue Date: | 2006 |
ISSN: | 1067-1927 1524-475X |
Statement of Responsibility: | Antiopi Varelias, Allison J. Cowin, Damian Adams, Richard H. C. Harries, Rodney D. Cooter, David A. Belford, Robert A. Fitridge and Timothy E. Rayner |
Abstract: | Matrix metalloproteinases (MMPs) and their tissue inhibitors play important roles in the wound-healing process. An imbalance in the expression of these molecules is thought to contribute to the failure of chronic ulcers to heal. We investigated whether a mitogenic bovine whey extract enriched with growth factors modulated the expression and activity of MMP-2 and -9, and the tissue inhibitor of MMP-2 (TIMP-2) in chronic leg ulcers. Wound fluids and biopsies were collected from chronic leg ulcer patients whose ulcers were treated topically for 4 weeks with placebo or mitogenic bovine whey extract at concentrations of 2.5, 10, and 20 mg/mL. The levels of MMP-2 and -9 in wound fluid samples was assessed by gelatin zymography and showed a decrease in active MMP-2 in the 2.5 and 10.0 mg/mL mitogenic bovine whey extract-treated ulcers compared with placebo (p<0.05). Immunohistochemical analysis of ulcer biopsies for MMP-2, -9, and TIMP-2 expression showed a reduction in the number of MMP-2–positive dermal fibroblasts in the mitogenic bovine whey extract-treated ulcers compared with pretreatment biopsies (p<0.05) that persisted over the course of the study. In contrast, a transient increase in the number of MMP-9– and TIMP-2–positive cells was observed in mitogenic bovine whey extract treated ulcer biopsies compared with pretreatment levels (p<0.05). These results show that topical application of mitogenic bovine whey extract was able to modulate the expression of MMP-2, -9, and TIMP-2 in chronic leg ulcers and that its constituent growth factors may have the potential to redress the proteolytic imbalance observed in nonhealing chronic ulcers. |
Keywords: | Animals Cattle Humans Leg Ulcer Chronic Disease Milk Proteins Tissue Inhibitor of Metalloproteinase-2 Mitogens Fluorescent Antibody Technique, Indirect Blotting, Western Treatment Outcome Electrophoresis, Polyacrylamide Gel Administration, Topical Analysis of Variance Prospective Studies Double-Blind Method Female Male Matrix Metalloproteinase 2 |
Description: | The definitive version is available at www.blackwell-synergy.com |
DOI: | 10.1111/j.1524-475X.2005.00085.x |
Published version: | http://dx.doi.org/10.1111/j.1524-475x.2005.00085.x |
Appears in Collections: | Aurora harvest 2 Medicine publications |
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