title: Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8).
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.
authors: Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, 33006 Oviedo, Spain.
authors: Ana
authors: A
authors: Gutiérrez-Fernández
authors: Masaki
authors: M
authors: Inada
authors: Milagros
authors: M
authors: Balbín
authors: Antonio
authors: A
authors: Fueyo
authors: Ana S
authors: AS
authors: Pitiot
authors: Aurora
authors: A
authors: Astudillo
authors: Kenji
authors: K
authors: Hirose
authors: Michiko
authors: M
authors: Hirata
authors: Steven D
authors: SD
authors: Shapiro
authors: Agnès
authors: A
authors: Noël
authors: Zena
authors: Z
authors: Werb
authors: Stephen M
authors: SM
authors: Krane
authors: Carlos
authors: C
authors: López-Otín
authors: Xose S
authors: XS
authors: Puente
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000502:physiology; D020022:Genetic Predisposition to Disease; D017403:In Situ Hybridization; D007249:Inflammation / Q000503:physiopathology*; D020784:Matrix Metalloproteinase 8 / Q000172:deficiency* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012878:Skin Neoplasms / Q000235:genetics; D014945:Wound Healing / Q000502:physiology*
chemical_list: D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9