Abstract
Several anti-angiogenic factors are derived from proteolytic processing of large molecules including endostatin from type XVIII collagen and angiostatin from plasminogen. In previous studies we showed that neostatin-7, the C-terminal 28kDa endostatin-spanning proteolytic fragment, is generated from the proteolytic action of matrix metalloproteinase matrilysin (MMP)-7 on type XVIII collagen. Now, we report a second member of the neostatin family of proteins, neostatin-14. Given the small quantities of neostatin-7 and -14 generated by the breakdown of naturally occurring collagen XVIII (using MMP-7 and -14, respectively), we used two other approaches to characterize the anti-angiogenic properties of these molecules: murine recombinant neostatin in vitro, and gene therapy. We demonstrate that murine recombinant neostatin-7 inhibits calf pulmonary artery endothelial cell proliferation and that microinjection of neostatin-7 and neostatin-14 naked DNA into the corneal stroma of mice results in significant reduction of basic fibroblast growth factor-induced corneal neovascularization. These results provide supportive evidence of the possible anti-angiogenic effect of neostatins.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / genetics
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Cattle
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Cell Proliferation / drug effects
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Collagen Type XVIII / chemistry*
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Collagen Type XVIII / genetics
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Collagen Type XVIII / metabolism
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Collagen Type XVIII / pharmacology
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Endostatins / chemistry
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Endostatins / genetics
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Endostatins / pharmacology
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Endothelium, Vascular / drug effects*
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Fibroblast Growth Factor 2 / antagonists & inhibitors
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Genetic Therapy
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Matrix Metalloproteinase 7 / chemistry
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Mice
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Molecular Sequence Data
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Neovascularization, Pathologic / genetics
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Neovascularization, Physiologic / drug effects*
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Peptide Fragments / chemistry
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Peptide Fragments / genetics
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Peptide Fragments / pharmacology*
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Pulmonary Artery / cytology
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
Substances
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Angiogenesis Inhibitors
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Collagen Type XVIII
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Endostatins
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Peptide Fragments
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Recombinant Proteins
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neostatin-14 protein, mouse
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neostatin-7 protein, mouse
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Fibroblast Growth Factor 2
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Matrix Metalloproteinase 7