BASIC FIBROBLAST GROWTH-FACTOR AND GROWTH-FACTOR RECEPTOR GENE-EXPRESSION IN 85-PERCENT O-2-EXPOSED RAT LUNG

Lungs exposed to elevated O-2 concentrations suffer an initial loss of type I pneumocytes, followed by a reparative type II pneumocyte hyper plasia. We hypothesized that type II pneumocyte hyperplasia after expo sure of young adult rats to 85% O-2 in vivo would be temporally relate d to 1) an increased concentration of intrapulmonary basic fibroblast growth factor (bFGF), a potent stimulator of type II pneumocyte DNA sy nthesis in vitro, and 2) an upregulation of pneumocyte receptors for b FGF (FGF-R). Increased rat lung bFGF mRNA, relative to air-exposed con trol animals, was observed at 4 days of exposure, with no increase at days 6 and 14 of exposure. Parallel changes were observed with bFGF re ceptor (flg) mRNA. Nuclear runoff assays confirmed increased transcrip tion of both bFGF and flg genes in response to 85% O-2, whereas increa sed translation at 6 days of exposure was confirmed by protein immunoa nalysis. Immunohistochemistry demonstrated a broad distribution of bFG F throughout the lung, including the alveolar epithelium, which increa sed after 6 and 14 days of exposure to 85% O-2. Our findings are compa tible with a role for bFGF in O-2-mediated pneumocyte hyperplasia.