Reference : Increased Inflammation Delays Wound Healing in Mice Deficient in Collagenase-2 (MMP-8)
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Increased Inflammation Delays Wound Healing in Mice Deficient in Collagenase-2 (MMP-8)
Gutierrez-Fernandez, A. [ > > ]
Inada, M. [ > > ]
Balbin, M. [ > > ]
Fueyo, A. [ > > ]
Pitiot, A. S. [ > > ]
Astudillo, A. [ > > ]
Hirose, K. [ > > ]
Hirata, M. [ > > ]
Shapiro, S. D. [ > > ]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Werb, Z. [ > > ]
Krane, S. M. [ > > ]
Lopez-Otin, C. [ > > ]
Puente, X. S. [ > > ]
FASEB Journal
Federation of American Society for Experimental Biology
Yes (verified by ORBi)
[en] neutrophil ; MMP-9 ; cancer ; protease ; degradome
[en] 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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