Epithelial-derived TGF-2 modulates basal and wound-healing subepithelial matrix homeostasis

epithelium influences the mesenchyme during dynamic processes such as embryogenesis, wound healing, fibrosis, and carcinogenesis. Since transforming growth factor- (TGF-) modulates these pro-cesses, we hypothesized that epithelial-derived TGF- also plays a critical role in maintaining the extracellular matrix at basal conditions. We utilized an in vitro model of the epithelial-mesenchymal trophic unit in the human airways to determine the role of epithelial-derived TGF- in modulating the extracellular matrix under basal and wound-healing conditions. When differentiated at an air-liquid interface, the human bronchial epithelium produces active TGF-2 at a concentra-tion of 50–70 pg/ml, whereas TGF-1 is undetectable. TGF-2 increases two- to threefold following scrape injury in a dose-depen-dent fashion and significantly enhances both -smooth muscle actin expression in the underlying collagen-embedded fibroblasts and se-cretion of tenascin-C into the matrix. Multiphoton microscopy dem