Allergen-Induced Airway Remodeling in Brown Norway Rats Structural and Metabolic Changes in Glycosaminoglycans

作者：Venkatesan Narayanan; Siddiqui Sana; Jo Taisuke; Martin James G; Ludwig Mara S^*

来源：American Journal of Respiratory Cell and Molecular Biology, 2012, 46(1): 96-105.

DOI：10.1165/rcmb.2011-0014OC

• airway remodeling
• glycosaminoglycans
• proteoglycans

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 HSGAGs were noted in OVA-challenged rats. The higher content and sulfation of CS/DS disaccharides was reflected by the increased expression of xylosyltransferase-I, beta 1,3-glucuronosyltransferase-I, chondroitin-4, and chondroitin-6 sulfotransferase genes and protein expression of xylosyltransferase-I and beta 1,3-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.

• 出版日期2012-1