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508655 
Journal Article 
The 'sweet' and 'bitter' involvement of glycosaminoglycans in lung diseases: pharmacotherapeutic relevance 
Papakonstantinou, E; Karakiulakis, G 
2009 
Yes 
British Journal of Pharmacology
ISSN: 0007-1188
EISSN: 1476-5381 
157 
7 
1111-1127 
English 
19508395 
WOS:000268260900002 
The extracellular matrix (ECM) plays a significant role in the structure and function of the lung. The ECM is a three-dimensional fibre mesh, comprised of various interconnected and intercalated macromolecules, among which are the glycosaminoglycans (GAG). GAG are long, linear and highly charged, heterogeneous polysaccharides that are composed of a variable number of repeating disaccharide units (macromolecular sugars) and most of them, as their name implies, have a sweet taste. In the lung, GAG support the structure of the interstitium, the subepithelial tissue and the bronchial walls, and are secreted in the airway secretions. Besides maintaining lung tissue structure, GAG also play an important role in lung function as they regulate hydration and water homeostasis, modulate the inflammatory response and influence lung tissue repair and remodelling. However, depending on their size and/or degree of sulphation, and their immobilization or solubilization in the ECM, specific GAG in the lung either live up to their sweet taste/name, supporting normal lung physiology, or they are associated to 'bitter' effects, related to lung pathology. The present review discusses the biological role of GAG in the lung as well as the involvement of these molecules in various respiratory diseases. Given the great structural diversity of GAG, understanding the changes in GAG expression that occur in lung diseases may lead to novel targets for pharmacological intervention in order to prevent and/or to treat a range of lung diseases. 
glycosaminoglycans; pulmonary fibrosis; pulmonary hypertension; asthma; COPD; hyaluronic acid; hyaluronic acid synthases; hyaluronidases; lung; diseases; hyaluronic acid receptors; pulmonary arterial-hypertension; smooth-muscle-cells; growth-factor-beta; chondroitin sulfate proteoglycan; exercise-induced; bronchoconstriction; mammalian hyaluronan synthases; chemokine; gene-expression; kappa-b translocation; protein-receptor-ii; heparan-sulfate