Abstract
Airway fibrosis is a characteristic feature of both asthma and COPD, in which fibroblasts are importantly involved. Increased activity of the cholinergic system may contribute to airway fibrosis, as muscarinic receptor stimulation has been shown to enhance collagen deposition by fibroblasts. The effects of muscarinic receptor stimulation on the expression profile of other extracellular matrix (ECM) proteins, however, remains to be established. To assess the effects of muscarinic receptor stimulation on ECM expression, MRC5 lung fibroblasts were stimulated for 24 h with increasing concentrations (10 nM – 100 μM) of the muscarinic receptor agonist methacholine in the absence and presence of the fibrogenic growth factor TGF-β1 (2 ng/ml), after which ECM gene expression was determined by quantitative PCR. The results demonstrate that methacholine concentration-dependently enhanced gene expression of the laminin α1 chain, whereas expression of the decorin gene was decreased. No effects of methacholine were observed on the gene expression of collagen I, collagen III, fibronectin, biglycan, versican or laminin α2, β1 and γ1 chains. In the presence of TGF-β1, methacholine (10 μM) enhanced the gene expression of fibronectin and collagen I. No additional effects of methacholine were observed on the expression of the other ECM genes investigated. Collectively, these results indicate that muscarinic receptor stimulation selectively changes the expression of specific ECM genes, which may contribute to the airway remodelling as observed in asthma and COPD.
- © 2011 ERS