Processing of types I and III procollagen in Ehlers-Danlos syndrome type VII.
The processing of types I and III procollagen was studied in skin fibroblast cultures from type VII A and B of the Ehlers-Danlos syndrome [EDS] and age-matched controls. Synthesis of collagenous proteins was significantly increased in EDS type VII B, and the activities of prolyl-4-hydroxylase and galactosylhydroxylysyl glucosyltransferase were slightly increased in these cell lines, reflecting increased biosynthesis of collagen. The synthesis of collagenous proteins was close to normal in EDS type VII A cells. The synthesis of type III procollagen per cell was increased, as also was the ratio of immunoreactive type III procollagen to total collagen production. The activity of type I procollagen amino-terminal proteinase was decreased in skin fibroblasts of type VII A and normal in those of type VII B relative to cell protein or DNA. Type III amino-terminal proteinase activity was of a level found in normal cells when expressed relative to the protein or DNA, and the release of type III amino-terminal propeptides was nevertheless not disturbed in these EDS type VII cell cultures. The results show that only the conversion of type I procollagen is defective in EDS type VII, and no general defect in procollagen processing can be found in EDS type VII as has been suggested in the case of dermatosparaxis, a connective tissue disorder in animals caused by disturbed procollagen conversion.
D002478:Cells, Cultured; D004535:Ehlers-Danlos Syndrome / Q000235:genetics*; D005964:Glucosyltransferases / Q000378:metabolism; D006801:Humans; D003012:Microbial Collagenase / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000235:genetics / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012867:Skin / Q000378:metabolism
D010446:Peptide Fragments; D011347:Procollagen; D011393:Procollagen-Proline Dioxygenase; D005964:Glucosyltransferases; C023247:UDP glucose-collagen glucosyltransferase; D003012:Microbial Collagenase