Extracellular matrix, integrins, and mesenchymal cell function in the airways.
Subepithelial fibrosis is one of the characteristic features of asthmatic airways. The fibrotic response includes an increase in volume occupied by extracellular matrix (ECM) tissue, and a change in the ECM composition favouring wound type collagens, fibronectin and a number of glycoproteins and proteoglycans normally associated with development. The altered ECM is likely to be deposited by the mesenchymal cells (including (myo) fibroblasts and smooth muscle) that are increased in number in asthmatic airways. In turn, the altered asthmatic ECM is likely to influence the function of the resident airway cells, and may be directly responsible for increasing proliferation, migration, ECM synthesis, inflammatory mediator release, and survival of resident mesenchymal cells. Therefore, the deposited ECM may perpetuate the disease phenotype. The different components of the ECM bi-directionally communicate with cells through a family of transmembrane receptors called integrins. Current research has begun to characterize: 1) the particular ECM components altered in airways disease; 2) the breadth of activity of different ECM components on airway cell function; and 3) the particular integrins responsible for mediating these effects. Further understanding of the role of integrins in transmitting responses of ECM in healthy or diseased airways may lead to novel targets for anti-asthma therapy.
Fernandes
Darren J
DJ
Department of Pharmacology, University of Melbourne, Parkville 3010, Australia. fernandesdj@yahoo.com.au
Bonacci
John V
JV
Stewart
Alastair G
AG
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D001980:Bronchi / Q000166:cytology* / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology*; D015398:Signal Transduction; D014132:Trachea / Q000166:cytology* / Q000378:metabolism
D018927:Anti-Asthmatic Agents; D016326:Extracellular Matrix Proteins; D016023:Integrins