Dermatan Sulfate Epimerase 1-Deficient Mice Have Reduced Content and Changed Distribution of Iduronic Acids in Dermatan Sulfate and an Altered Collagen Structure in Skin
Open Access
- 1 October 2009
- journal article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 29 (20), 5517-5528
- https://doi.org/10.1128/mcb.00430-09
Abstract
Dermatan sulfate epimerase 1 (DS-epi1) and DS-epi2 convert glucuronic acid to iduronic acid in chondroitin/dermatan sulfate biosynthesis. Here we report on the generation of DS-epi1-null mice and the resulting alterations in the chondroitin/dermatan polysaccharide chains. The numbers of long blocks of adjacent iduronic acids are greatly decreased in skin decorin and biglycan chondroitin/dermatan sulfate, along with a parallel decrease in iduronic-2-O-sulfated-galactosamine-4-O-sulfated structures. Both iduronic acid blocks and iduronic acids surrounded by glucuronic acids are also decreased in versican-derived chains. DS-epi1-deficient mice are smaller than their wild-type littermates but otherwise have no gross macroscopic alterations. The lack of DS-epi1 affects the chondroitin/dermatan sulfate in many proteoglycans, and the consequences for skin collagen structure were initially analyzed. We found that the skin collagen architecture was altered, and electron microscopy showed that the DS-epi1-null fibrils have a larger diameter than the wild-type fibrils. The altered chondroitin/dermatan sulfate chains carried by decorin in skin are likely to affect collagen fibril formation and reduce the tensile strength of DS-epi1-null skin.Keywords
This publication has 52 references indexed in Scilit:
- Two Dermatan Sulfate Epimerases Form Iduronic Acid Domains in Dermatan SulfatePublished by Elsevier BV ,2009
- Type XIV Collagen Regulates FibrillogenesisPublished by Elsevier BV ,2009
- Collagen-binding proteoglycan fibromodulin can determine stroma matrix structure and fluid balance in experimental carcinomaProceedings of the National Academy of Sciences of the United States of America, 2007
- The Decorin Sequence SYIRIADTNIT Binds Collagen Type IPublished by Elsevier BV ,2007
- Heparin Cofactor II Modulates the Response to Vascular InjuryArteriosclerosis, Thrombosis, and Vascular Biology, 2007
- Placental dermatan sulfate: isolation, anticoagulant activity, and association with heparin cofactor IIBlood, 2006
- Direct measurement of the rupture force of single pair of decorin interactionsBiochemical and Biophysical Research Communications, 2005
- Targeted Disruption of a Murine Glucuronyl C5-epimerase Gene Results in Heparan Sulfate Lacking l-Iduronic Acid and in Neonatal LethalityPublished by Elsevier BV ,2003
- A novel CpG-associated brain-expressed candidate gene for chromosome 18q-linked bipolar disorderMolecular Psychiatry, 2003
- The structure of interfibrillar proteoglycan bridges (‘shape modules’) in extracellular matrix of fibrous connective tissues and their stability in various chemical environmentsJournal of Anatomy, 1998