TAILIEUCHUNG - Báo cáo khoa học: The glycosaminoglycan chain of decorin plays an important role in collagen fibril formation at the early stages of fibrillogenesis

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 gly-cosaminoglycan side chain. | ễFEBS Journal The glycosaminoglycan chain of decorin plays an important role in collagen fibril formation at the early stages of fibrillogenesis Claus Ruhland1 Elke Schonherr2 Horst Robenek3 Uwe Hansen1 Renato V. lozzo4 Peter Bruckner1 and Daniela G. Seidler1 1 Department of PhysiologicalChemistry and Pathobiochemistry University of Munster Germany 2 Matrix Biology and Tissue Repair Research Unit Cardiff University UK 3 Leibniz-Institute of Arteriosclerosis Research University of Munster Germany 4 Department of Pathology Anatomy and Cell Biology and the KimmelCancer Center Thomas Jefferson University Philadelphia PA USA Keywords 3D model collagen fibrils decorin-null fibroblasts glycosaminoglycan chain in vitro fibrillogenesis Correspondence D. G. Seidler Department of Physiological Chemistry and Pathobiochemistry Waldeyerstr. 15 48149 Munster Germany Fax 49 251 83 55596 Tel 49 251 83 55573 E-mail dgseidle@ Received 18 May 2007 accepted 22 June 2007 doi 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 fibril-logenesis. 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 .

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