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Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8).

Authors
  • Gutiérrez-Fernández, Ana
  • Inada, Masaki
  • Balbín, Milagros
  • Fueyo, Antonio
  • Pitiot, Ana S
  • Astudillo, Aurora
  • Hirose, Kenji
  • Hirata, Michiko
  • Shapiro, Steven D
  • Noël, Agnès
  • Werb, Zena
  • Krane, Stephen M
  • López-Otín, Carlos
  • Puente, Xose S
Type
Published Article
Journal
The FASEB Journal
Publisher
Federation of American Society for Experimental Biology
Publication Date
Aug 01, 2007
Volume
21
Issue
10
Pages
2580–2591
Identifiers
PMID: 17392479
Source
Medline
License
Unknown

Abstract

Matrix metalloproteinases (MMPs) have been implicated in numerous tissue-remodeling processes. The finding that mice deficient in collagenase-2 (MMP-8) are more susceptible to develop skin cancer, prompted us to investigate the role of this protease in cutaneous wound healing. We have observed a significant delay in wound closure in MMP8-/- mice and an altered inflammatory response in their wounds, with a delay of neutrophil infiltration during the first days and a persistent inflammation at later time points. These changes were accompanied by alterations in the TGF-beta1 signaling pathway and by an apoptosis defect in MMP8-/- mice. The delay in wound healing observed in MMP8-/- mice was rescued by bone marrow transplantation from wild-type mice. Analysis of other MMPs showed that MMP8-/- mice had a significant increase in the expression of MMP-9, suggesting that both proteases might act coordinately in this process. This possibility was further supported by the novel finding that MMP-8 and MMP-9 form specific complexes in vivo. Taken together, these data indicate that MMP-8 participates in wound repair by contributing to the resolution of inflammation and open the possibility to develop new strategies for treating wound healing defects.

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