First Author | Gutiérrez-Fernández A | Year | 2007 |
Journal | FASEB J | Volume | 21 |
Issue | 10 | Pages | 2580-91 |
PubMed ID | 17392479 | Mgi Jnum | J:134846 |
Mgi Id | MGI:3789877 | Doi | 10.1096/fj.06-7860com |
Citation | Gutierrez-Fernandez A, et al. (2007) Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8). FASEB J 21(10):2580-91 |
abstractText | 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. |