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Matrix Proteolytic Activity During Wound Healing: Modulation by Acute Ethanol Exposure

Authors

  • Katherine A. Radek,

    1. Alcohol Research Program, Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois
    2. Division of Molecular and Cellular Biochemistry, Loyola University Medical Center, Maywood, Illinois
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  • Elizabeth J. Kovacs,

    1. Alcohol Research Program, Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois
    2. Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, Maywood, Illinois
    3. Department of Surgery, Loyola University Medical Center, Maywood, Illinois
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  • Luisa A. DiPietro

    1. Center for Wound Healing and Tissue Regeneration, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois
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  • This research was supported by National Institutes of Health grants F31 AA 15277-01A1 (KAR), RO1-GM-55238 (LAD), RO1-GM-50875 (LAD), and the Dr. Ralph and Marian C. Falk Medical Research Trust (LAD, EJK).

Reprint requests: Luisa A. DiPietro, DDS, PhD, Center for Wound Healing and Tissue Regeneration, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina, Chicago, IL 60612; Fax: 312-996-0943; Email: ldipiet@uic.edu

Abstract

Background: Clinical studies demonstrate that intoxicated patients exhibit an increased incidence of wound healing complications. Previous studies in a murine excisional wound model revealed that acute ethanol exposure impairs the wound healing response, causing decreased angiogenesis and a significant reduction in wound collagen content.

Methods: Using the same murine model of excisional wounding, we examined the effect of a single dose of ethanol on the overall collagen content and collagen type I and type III mRNA expression, transforming growth factor-β (TGF-β) production, and levels of several components of the extracellular matrix proteolytic cascade.

Results: Wounds from ethanol-treated mice exhibited a significant decrease in collagen and in the production of collagen type I mRNA compared with saline controls. Exposure to ethanol also caused significant increase in wound TGF-β by day 2 after injury (1.69 ± 0.29 vs 12.34 ± 3.97 pg/μg protein, p<0.01). In addition, wounds from mice exposed to ethanol had significantly increased levels of active urokinase plasminogen activator at day 7, (205.10 ± 48.79 vs 642.70 ± 159.80 pg/μg protein, p<0.001). The level of matrix metalloproteinase-8, a collagen type I proteinase, was 2.2-fold higher in wounds of ethanol-treated mice compared with control at day 7 (p<0.05).

Conclusions: These studies demonstrate that a single dose of ethanol decreases collagen production, increases the production of TGF-β and increases levels of matrix degrading enzymes. This alteration in protease balance may partially explain the impaired wound healing that follows acute alcohol intoxication.

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