EPITHELIAL-MESENCHYMAL INTERACTION AND INSULIN-LIKE GROWTH FACTORS IN HYPEROXIC LUNG INJURY

Abstract

To investigate the role of epithelial-mesenchymal interaction on oxygen-induced lung injury, we used a coculture model with lung fibroblasts (FB) embedded between 2 layers of collagen gel with and without human tracheobronchial epithelial cells (HTBE), and studied the effect of hyperoxia on the directed migration of FB towards epithelial cells and proliferation of fetal lung FB. The expression of insulin-like growth factor (IGF)-I, -II, and -IIR mRNAs and proteins was studied in FB and HTBE cells cultured separately in 95% oxygen and 5% CO2 for 48 hours. There was a significant increase in directional migration of FB in coculture with epithelial cells when exposed to 95% oxygen and 5% CO2 (P =. 04 compared to cocultures without oxygen exposure). Hyperoxia stimulated the proliferation of fibroblasts cocultured with HTBE cells (0.75 +/- 0.05 X 106 cells per well) as compared to control (0.47 +/- 0.03 X 106 cells per well; P =. 01). This was inhibited by anti-IGF-I antibody (69 +/- 2% of hyperoxia alone; P =. 002). Western blot showed a significant increase in IGF-I protein in epithelial cells (P =. 02). IGF-I mRNA was increased in HTBE cells after hyperoxia (P =. 003). In conclusion, HTBE cells modulate lung FB migration and proliferation in response to hyperoxia exposure. This is mediated in part by IGF-I produced by epithelial cells.