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: Narayanan Venkatesan, Sana Siddiqui, Taisuke Jo, James G Martin, Mara S Ludwig
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 46 Issue 1 Pg. 96-105 (Jan 2012) ISSN: 1535-4989 [Electronic] United States
• PMID: 21852687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Allergens
• Chondroitin Sulfate Proteoglycans
• Disaccharides
• Glycosaminoglycans
• Somatomedins
• smooth muscle actin, rat
• Ovalbumin
• glucuronyltransferase GlcAT-1
• Glucuronosyltransferase
• Pentosyltransferases
• Sulfotransferases

Topics

• Actins (genetics, metabolism)
• Airway Remodeling (drug effects, immunology)
• Allergens (immunology)
• Animals
• Asthma (genetics, immunology, metabolism)
• Bronchoalveolar Lavage Fluid (cytology, immunology)
• Chondroitin Sulfate Proteoglycans (metabolism)
• Disaccharides (metabolism)
• Glucuronosyltransferase (genetics, metabolism)
• Glycosaminoglycans (metabolism)
• Lung (metabolism, pathology)
• Male
• Ovalbumin (immunology)
• Pentosyltransferases (genetics, metabolism)
• Rats
• Rats, Inbred BN
• Somatomedins (metabolism)
• Sulfotransferases (metabolism)
• Up-Regulation
• UDP Xylose-Protein Xylosyltransferase