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Increased inflammation delays wound healing in mice deficient in collagenase‐2 (MMP‐8)
Author(s) -
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.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-7860com
Subject(s) - proteases , matrix metalloproteinase , wound healing , inflammation , collagenase , apoptosis , immunology , cancer research , medicine , chemistry , enzyme , biochemistry
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‐β1 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 coordi‐nately 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.—Gutierrez‐Fernandez, A., Inada, M., Balbín, M., Fueyo, A., Pitiot, A. S., Astudillo, A., Hirose, K., Hirata, M., Shapiro, S. D., Noel, A., Werb, Z., Krane, S. M. Lopez‐Otín, C., Puente, X. S. FASEB J. 21, 2580–2591 (2007)