title: Collagen fibril formation. A new target to limit fibrosis.
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.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Chung
authors.forename: Andrzej
authors.initials: A
authors.lastname: Steplewski
authors.forename: Kee Yang
authors.initials: KY
authors.lastname: Chung
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.forename: Andrzej
authors.initials: A
authors.lastname: Fertala
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D003094:Collagen / Q000737:chemistry*; D024042:Collagen Type I / Q000737:chemistry*; D000939:Epitopes / Q000737:chemistry; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007627:Keloid / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000737:chemistry; D012867:Skin / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D000939:Epitopes; D010455:Peptides; D003094:Collagen; D008666:Metalloendopeptidases; C525705:BMP1 protein, human; C525707:Bmp1 protein, mouse; D055395:Bone Morphogenetic Protein 1