RATIONALE: Airway remodeling is considered a major hallmark of asthma, but a clear understanding of the mechanisms underlining this phenomenon is lacking. We therefore investigated if acquired functional and phenotypic changes in airway fibroblasts could contribute to the development of airway remodeling using a murine model of asthma. METHODS: The mouse model of asthma was established by sensitizing and challenging female BALB/c mice with ovalbumin. DNA microarray experiments were performed to determine differential gene expression. In vitro release of TGF-β1, VEGF, and fibronectin was measured by ELISA. Collagen gel contraction assays were performed to simulate the effect of fibroblasts on actin contraction. α-SMA expression was measured by Western blot. Fibroblast cell migration ability was assessed by using Boyden chamber. Finally, fibroblast proliferation rate was determined. RESULTS: Many genes were differentially expressed when fibroblasts from “asthmatic” versus control mice were compared. Airway fibroblasts from asthmatic mice displayed significant increase in collagen gel contraction ability, chemotactic activity, α-SMA expression, and growth factors (TGF-β1, VEGF, fibronectin) release in comparison to control mice. Moreover, fibroblasts from asthmatic mice proliferated at more than twice the doubling rate of fibroblasts from control mice. CONCLUSIONS: These results revealed that, at least in an animal model of asthma, asthmatic fibroblasts acquire a distinct phenotype that differs from control fibroblasts. The increased pro-fibrotic activity and mediator release by asthmatic fibroblasts suggest that these cells could play an important role in the development of airway remodeling in asthma.