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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
Statement of
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
RMID: 0020060194
DOI: 10.1111/j.1524-475X.2005.00085.x
Appears in Collections:Medicine publications

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