title: Allergen-induced airway remodeling in brown norway rats: structural and metabolic changes in glycosaminoglycans.
abstract: Increased proteoglycan (PG) deposition is a feature of airway remodeling in asthma. Glycosaminoglycans (GAGs) mediate many of the biological and mechanical properties of PGs by providing docking sites through their carbohydrate chains to bioactive ligands; therefore, it is imperative to define structural and metabolic changes of GAGs in asthma. Using a Brown Norway (BN) ovalbumin (OVA)-sensitized and -challenged rat model to induce airway remodeling, we found excessive deposition of chondroitin/dermatan (CS/DS)-, heparan (HS), and keratan (KS) sulfate GAGs in the airways and bronchoalveolar lavage cells of OVA-challenged rats. Disaccharide composition of CS/DS of OVA-challenged rats was significantly different compared with saline-treated (SAL) control rats, with increased levels of 0-, 6-, and 4-sulfated disaccharides. Increases in the amount and a change in the proportion of CS/DS versus HS GAGs were noted in OVA-challenged rats. The higher content and sulfation of CS/DS disaccharides was reflected by the increased expression of xylosyltransferase-I, β1,3-glucuronosyltransferase-I, chondroitin-4, and chondroitin-6 sulfotransferase genes and protein expression of xylosyltransferase-I and β1,3-glucuronosyltransferase-I in OVA-challenged rats. Genes encoding the core proteins of the CS/DS and KS-containing PGs, such as versican, biglycan, decorin, and lumican, were overexpressed in OVA-challenged rats. Our results suggest that GAG biosynthetic enzymes may be involved in the altered expression of GAGs in the airways and are potential targets for inhibiting excess PG-GAG deposition and the airway remodeling process in asthma.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Venkatesan
authors.forename: Sana
authors.initials: S
authors.lastname: Siddiqui
authors.forename: Taisuke
authors.initials: T
authors.lastname: Jo
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
authors.forename: Mara S
authors.initials: MS
authors.lastname: Ludwig
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D056151:Airway Remodeling / Q000187:drug effects* / Q000276:immunology; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D004187:Disaccharides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010430:Pentosyltransferases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D013002:Somatomedins / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism; D015854:Up-Regulation; D000097608:UDP Xylose-Protein Xylosyltransferase
chemical_list: D000199:Actins; D000485:Allergens; D011508:Chondroitin Sulfate Proteoglycans; D004187:Disaccharides; D014453:Glucuronosyltransferase; D006025:Glycosaminoglycans; D010047:Ovalbumin; D010430:Pentosyltransferases; D013002:Somatomedins; D015238:Sulfotransferases; D000097608:UDP Xylose-Protein Xylosyltransferase; C498862:Acta2 protein, rat; C067806:glucuronyltransferase GlcAT-1