title: MT1-MMP cleavage of the antiangiogenic proteoglycan decorin: role in corneal angiogenesis.
abstract: OBJECTIVE
  Decorin is a small chondroitin sulfate proteoglycan that inhibits vascular endothelial cell migration and tube formation. Membrane type 1-matrix metalloproteinase (MT1-MMP) has been shown to be an important angiogenic enzyme in the cornea. We evaluated the specific role of MT1-MMP in decorin cleavage in the cornea.
  
  
  METHODS
  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 the stimulatory effect of MT1-MMP on vascular endothelial cells in vitro. Corneal micropocket assays using basic fibroblast growth factor (bFGF) were used to assess changes in the levels of decorin and MT1-MMP.
  
  
  RESULTS
  MT1-MMP cleaves decorin in a time- and concentration-dependent manner in vitro. MT1-MMP levels were upregulated after in vivo bFGF pellet implantation in the cornea, and decorin cleavage products were detected in bFGF-implanted corneas but not in normal corneas. MT1-MMP reduced the inhibitory effects of decorin on aortic ring tube formation in vitro.
  
  
  CONCLUSIONS
  MT1-MMP may play an essential role in angiogenesis through proteolytic processing of decorin in the cornea.
authors.affiliation: Department of Ophthalmology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan. mimurat-tky@umin.ac.jp
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Mimura
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Chang
authors.forename: Tae-Im
authors.initials: TI
authors.lastname: Kim
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Onguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakimoto
authors.forename: Dimitri T
authors.initials: DT
authors.lastname: Azar
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003315:Cornea / Q000378:metabolism*; D016510:Corneal Neovascularization / Q000378:metabolism*; D058575:Decorin / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D053511:Matrix Metalloproteinase 14 / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D058575:Decorin; D016222:Fibroblast Growth Factor 2; D053511:Matrix Metalloproteinase 14