title: Altered posttranslational modifications of collagen in keloid.
abstract: Keloid is a tissue with an excessive accumulation of collagen. In this study, we have partially characterized post-translational modifications of type I collagen in human keloid in order to pursue their potential involvement in this pathology. The levels of lysyl hydroxylation of the helical portions of alpha 1 and alpha 2 chains of type I collagen in keloid were significantly higher than those of normal, while the levels of prolyl hydroxylation were identical between these two groups. The contents of the major reducible cross-links in dermal collagen, dehydro-hydroxylysinonorleucine and dehydro-histidinohydroxymero-desmosine, were both significantly higher in keloids (up to sixfold) than those of normal. In addition, significant amounts of hydroxylysine-aldehyde derived cross-links that are characteristic of skeletal tissue collagens, dehydro-dihydroxylysinonorleucine (about 0.3 mole/mole of collagen) and pyridinoline (about 0.1 mole/mole of collagen), were found in keloids. These results indicate that keloid-forming cells are phenotypically different from those in normal dermis and that the collagen produced is highly cross-linked. The increased cross-linking provides the fibrils with more stability that may result in an accumulation of collagen.
authors.affiliation: Dental Research Center, University of North Carolina at Chapel Hill 27599-7455, USA.
authors.forename: K
authors.initials: K
authors.lastname: Uzawa
authors.forename: M K
authors.initials: MK
authors.lastname: Marshall
authors.forename: E P
authors.initials: EP
authors.lastname: Katz
authors.forename: H
authors.initials: H
authors.lastname: Tanzawa
authors.forename: H N
authors.initials: HN
authors.lastname: Yeowell
authors.forename: M
authors.initials: M
authors.lastname: Yamauchi
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000032:analysis; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism*; D003432:Cross-Linking Reagents; D003895:Desmosine / Q000031:analogs & derivatives / Q000032:analysis; D004151:Dipeptides / Q000032:analysis; D006639:Histidine / Q000031:analogs & derivatives / Q000032:analysis; D006801:Humans; D006900:Hydroxylation; D006901:Hydroxylysine / Q000032:analysis; D006909:Hydroxyproline / Q000032:analysis; D007627:Keloid / Q000378:metabolism*; D008875:Middle Aged; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D012867:Skin / Q000378:metabolism
chemical_list: D000596:Amino Acids; D003432:Cross-Linking Reagents; D004151:Dipeptides; C075793:histidinohydroxylysinonorleucine; D003895:Desmosine; C007428:5,5'-dihydroxylysylnorleucine; C010991:delta-hydroxylysylnorleucine; D006901:Hydroxylysine; D006639:Histidine; C002527:histidinohydroxymerodesmosine; C015484:pyridinoline; C036020:deoxypyridinoline; D003094:Collagen; D006909:Hydroxyproline