BACKGROUND/AIMS: Decorin has been shown to have antiangiogenic properties. In this study, we evaluate the involvement of membrane type 1-matrix metalloproteinase (MT1-MMP), a proangiogenic enzyme, in decorin cleavage in the cornea. METHODS: MT1-MMP expression was confirmed immunohistochemically in keratocytes and immortalized corneal fibroblast cell lines. Corneal micropockets of bFGF were used to assess the expression of decorin and MT1-MMP. Western blotting was used to evaluate decorin degradation by MT1-MMP. Aortic ring tube formation assays were used to assay the inhibitory effect of decorin and stimulatory effect of MT1-MMP on vascular endothelial cells in vitro. RESULTS: We show that MT1-MMP expression is upregulated following bFGF pellet implantation in the cornea in vivo, and that MT1-MMP cleaves decorin in a time- and concentration-dependent manner in vitro. Furthermore, the addition of MT1-MMP reduces the inhibitory effects of decorin on aortic ring tube formation in vitro. Cleavage of decorin by MT1-MMP-deficient corneal cell lysates is diminished relative to that by wild-type corneal cell lysates, and an MT1-MMP knockin restores decorin processing in vitro. CONCLUSION: The proangiogenic role of MT1-MMP in the cornea may be mediated, in part, by facilitated cleavage of corneal decorin. Copyright 2009 S. Karger AG, Basel.
BACKGROUND/AIMS: Decorin has been shown to have antiangiogenic properties. In this study, we evaluate the involvement of membrane type 1-matrix metalloproteinase (MT1-MMP), a proangiogenic enzyme, in decorin cleavage in the cornea. METHODS:MT1-MMP expression was confirmed immunohistochemically in keratocytes and immortalized corneal fibroblast cell lines. Corneal micropockets of bFGF were used to assess the expression of decorin and MT1-MMP. Western blotting was used to evaluate decorin degradation by MT1-MMP. Aortic ring tube formation assays were used to assay the inhibitory effect of decorin and stimulatory effect of MT1-MMP on vascular endothelial cells in vitro. RESULTS: We show that MT1-MMP expression is upregulated following bFGF pellet implantation in the cornea in vivo, and that MT1-MMP cleaves decorin in a time- and concentration-dependent manner in vitro. Furthermore, the addition of MT1-MMP reduces the inhibitory effects of decorin on aortic ring tube formation in vitro. Cleavage of decorin by MT1-MMP-deficient corneal cell lysates is diminished relative to that by wild-type corneal cell lysates, and an MT1-MMP knockin restores decorin processing in vitro. CONCLUSION: The proangiogenic role of MT1-MMP in the cornea may be mediated, in part, by facilitated cleavage of corneal decorin. Copyright 2009 S. Karger AG, Basel.
Authors: L Nelimarkka; H Salminen; T Kuopio; S Nikkari; T Ekfors; J Laine; L Pelliniemi; H Järveläinen Journal: Am J Pathol Date: 2001-02 Impact factor: 4.307
Authors: Z Zhou; S S Apte; R Soininen; R Cao; G Y Baaklini; R W Rauser; J Wang; Y Cao; K Tryggvason Journal: Proc Natl Acad Sci U S A Date: 2000-04-11 Impact factor: 11.205
Authors: Kevin B Hotary; Edward D Allen; Peter C Brooks; Nabanita S Datta; Michael W Long; Stephen J Weiss Journal: Cell Date: 2003-07-11 Impact factor: 41.582