Matrix metalloproteinase-8 overexpression prevents proper tissue repair.

Published on Nov 1, 2011in Surgery3.356
· DOI :10.1016/J.SURG.2011.06.016
Patricia L Danielsen7
Estimated H-index: 7
(UCPH: University of Copenhagen),
Anders Vedel Holst3
Estimated H-index: 3
(UCPH: University of Copenhagen)
+ 8 AuthorsMagnus S. Ågren42
Estimated H-index: 42
(UCPH: University of Copenhagen)
Background The collagenolytic matrix metalloproteinase-8 (MMP-8) is essential for normal tissue repair but is often overexpressed in wounds with disrupted healing. Our aim was to study the impact of a local excess of this neutrophil-derived proteinase on wound healing using recombinant adenovirus-driven transduction of full-length Mmp8 (AdMMP-8). Methods The effect of MMP-8 overexpression was evaluated in dermal fibroblasts and in two wound healing models in male Wistar rats: subcutaneously positioned ePTFE catheters and linear incisional skin wounds. Results Fibroblasts transduced with AdMMP-8 secreted MMP-8 with type I collagenolytic activity that could be blocked by a selective MMP-8 inhibitor. AdMMP-8 (5 × 10 10 viral particles) administered in homologous fibrin increased MMP-8 mRNA ( P P P P Conclusion These results demonstrate that superphysiologic levels of the proteinase MMP-8 can result in decreased collagen and lead to impaired wound healing. This observation makes MMP-8 a potential drug target in compromised human wound healing associated with MMP-8 overexpression.
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