期刊
JOURNAL OF VASCULAR RESEARCH
卷 46, 期 6, 页码 541-550出版社
KARGER
DOI: 10.1159/000226222
关键词
Corneal neovascularization; Angiogenesis; Metalloproteinase; MMP-14; Membrane type 1-matrix metalloproteinase; Decorin; Extracellular matrix
资金
- National Institutes of Health [EY10101, P30EY001792, EY14048]
- NATIONAL EYE INSTITUTE [R29EY010101, P30EY001792, R01EY010101, R01EY014048] Funding Source: NIH RePORTER
- Grants-in-Aid for Scientific Research [21659398] Funding Source: KAKEN
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 (C) 2009 S. Karger AG, Basel
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