Effect of extracellular matrix composition on airway epithelial cell and fibroblast structure: implications for airway remodeling in asthma.
BACKGROUND
Airway remodeling in asthma is characterized by structural changes to the airways including extracellular matrix (ECM) deposition and epithelial metaplasia. Extracellular matrix deposition in the subepithelial region may play an important role in modulation of epithelial cell and fibroblast structure and function because it lies in immediate contact with these cell types and exists within the functional epithelial mesenchymal trophic unit.


OBJECTIVE
To investigate the effect of aberrant ECM components on airway epithelial cells and fibroblasts and the relationship among subepithelial ECM deposition, other remodeling changes, and airway hyperresponsiveness.


METHODS
BEAS-2B human airway epithelial cells and WI-38 human airway fibroblast cells were cultured on various ECM protein substrates (Matrigel, representing normal basement membrane matrix, or aberrant matrix proteins collagen I, collagen III, and fibronectin). Airway remodeling changes were determined using morphometry in sections from a murine model of chronic allergic airway disease. Airway reactivity to methacholine was determined, and these parameters correlated.


RESULTS
Abnormal ECM substrates induced epithelial and fibroblast proliferation and altered the cell morphology of both human airway epithelial cells and fibroblasts when compared with normal basement membrane ECM. Subepithelial matrix deposition in the mouse correlated with epithelial thickness, but only weak correlations were noted among the other parameters.


CONCLUSIONS
We have demonstrated that ECM may affect the growth of airway epithelial cells and fibroblasts in vitro and may influence epithelial thickness in the mouse. These findings may have implications for understanding the pathogenesis of asthma and future therapeutic targeting of airway remodeling.
Department of Allergy and Immunology, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
Simon G
SG
Royce
Liling
L
Tan
Alicia A
AA
Koek
Mimi L K
ML
Tang
D000818:Animals; D001249:Asthma / Q000209:etiology / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D024042:Collagen Type I / Q000494:pharmacology; D024061:Collagen Type III / Q000494:pharmacology; D004195:Disease Models, Animal; D004338:Drug Combinations; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000473:pathology / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005353:Fibronectins / Q000494:pharmacology; D020397:Goblet Cells / Q000473:pathology; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008168:Lung / Q000473:pathology*; D051379:Mice; D011509:Proteoglycans / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000473:pathology / Q000503:physiopathology; D020545:Respiratory Mucosa / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D024042:Collagen Type I; D024061:Collagen Type III; D004338:Drug Combinations; D005353:Fibronectins; D007797:Laminin; D011509:Proteoglycans; D053773:Transforming Growth Factor beta1; C059485:matrigel; D003094:Collagen