Collagen fibril formation. A new target to limit fibrosis.
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.
Chung
Hye Jin
HJ
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Steplewski
Andrzej
A
Chung
Kee Yang
KY
Uitto
Jouni
J
Fertala
Andrzej
A
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
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