MT1-MMP Cleavage of the Antiangiogenic Proteoglycan Decorin: Role in Corneal Angiogenesis

Abstract

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. 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. 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. MT1-MMP may play an essential role in angiogenesis through proteolytic processing of decorin in the cornea.