title: The glycosaminoglycan chain of decorin plays an important role in collagen fibril formation at the early stages of fibrillogenesis.
abstract: Decorin is a multifunctional small leucine-rich proteoglycan involved in the regulation of collagen fibrillogenesis. In patients with a variant of Ehlers-Danlos syndrome, about half of the secreted decorin lacks the single glycosaminoglycan side chain. Notably, these patients have a skin-fragility phenotype that resembles that of decorin null mice. In this study, we investigated the role of glycanated and unglycanated decorin on collagen fibrillogenesis. Glycosaminoglycan-free decorin, generated by mutating Ser4 of the mature protein core into Ala (DCN-S4A), showed reduced inhibition of fibrillogenesis compared with the decorin proteoglycan. Interestingly, using a 3D matrix generated by decorin-null fibroblasts, an increase in fibril diameter was found after the addition of decorin, and even greater effects were observed with DCN-S4A. To avoid potential side effects of artificial tags, adenoviruses containing decorin and DCN-S4A were used to transduce decorin-null fibroblasts prior to matrix formation. Both molecules were efficiently incorporated into the matrix, with no changes in collagen composition and network formation, or altered expression of the related proteoglycan biglycan. Both decorin and DCN-S4A mutants increased the collagen fibril diameter, with the latter showing the most prominent effects. These data show that at early stages of fibrillogenesis, the glycosaminoglycan chain of decorin has a reducing effect on collagen fibril diameter.
authors.affiliation: Department of Physiological Chemistry and Pathobiochemistry, University of Münster, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Rühland
authors.forename: Elke
authors.initials: E
authors.lastname: Schönherr
authors.forename: Horst
authors.initials: H
authors.lastname: Robenek
authors.forename: Uwe
authors.initials: U
authors.lastname: Hansen
authors.forename: Renato V
authors.initials: RV
authors.lastname: Iozzo
authors.forename: Peter
authors.initials: P
authors.lastname: Bruckner
authors.forename: Daniela G
authors.initials: DG
authors.lastname: Seidler
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D058578:Biglycan; D015152:Blotting, Northern; D002460:Cell Line; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism* / Q000648:ultrastructure; D058575:Decorin; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006025:Glycosaminoglycans / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020894:Microfibrils / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D009154:Mutation; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C546884:BGN protein, human; C546885:Bgn protein, mouse; D058578:Biglycan; C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D011509:Proteoglycans; D003094:Collagen