Abstract
We present a concept for reducing formation of fibrotic deposits by inhibiting self-assembly of collagen molecules into fibrils, a main component of fibrotic lesions. Employing monoclonal antibodies that bind to the telopeptide region of a collagen molecule, we found that blocking telopeptide-mediated collagen/collagen interactions reduces the amount of collagen fibrils accumulated in vitro and in keloid-like organotypic constructs. We conclude that inhibiting extracellular steps of the fibrotic process provides a novel approach to limit fibrosis in a number of tissues and organs.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antibodies, Monoclonal / chemistry
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Bone Morphogenetic Protein 1
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Bone Morphogenetic Proteins / metabolism
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Collagen / chemistry*
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Collagen Type I / chemistry*
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Epitopes / chemistry
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Extracellular Matrix / metabolism
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Fibroblasts / metabolism
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Fibrosis
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Humans
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Keloid / metabolism
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Metalloendopeptidases / metabolism
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Mice
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Mice, Nude
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Peptides / chemistry
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Skin / metabolism
Substances
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Antibodies, Monoclonal
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Bone Morphogenetic Proteins
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Collagen Type I
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Epitopes
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Peptides
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Collagen
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Metalloendopeptidases
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BMP1 protein, human
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Bmp1 protein, mouse
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Bone Morphogenetic Protein 1