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MT1-MMP-mediated cleavage of decorin in corneal angiogenesis

Authors
 Tatsuya Mimura  ;  Kyu Yeon Han  ;  Tatsuya Onguchi  ;  Jin-Hong Chang  ;  Tae-im Kim  ;  Takashi Kojima  ;  Zhongjun Zhou  ;  Dimitri T. Azar 
Citation
 JOURNAL OF VASCULAR RESEARCH, Vol.46(6) : 541-550, 2009 
Journal Title
 JOURNAL OF VASCULAR RESEARCH 
ISSN
 1018-1172 
Issue Date
2009
MeSH
Animals ; Aorta/enzymology ; Cell Line ; Cornea/enzymology* ; Corneal Neovascularization/chemically induced ; Corneal Neovascularization/enzymology* ; Culture Media, Conditioned/metabolism ; Decorin ; Dipeptides/pharmacology ; Disease Models, Animal ; Extracellular Matrix Proteins/metabolism* ; Fibroblast Growth Factor 2 ; Kinetics ; Matrix Metalloproteinase 14/deficiency ; Matrix Metalloproteinase 14/genetics ; Matrix Metalloproteinase 14/metabolism* ; Matrix Metalloproteinase Inhibitors ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Protease Inhibitors/pharmacology ; Proteoglycans/metabolism* ; Recombinant Proteins/metabolism ; Tissue Culture Techniques ; Transfection
Abstract
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.
Files in This Item:
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DOI
10.1159/000226222
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Tae Im(김태임) ORCID logo https://orcid.org/0000-0001-6414-3842
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/165022
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