AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 3 455-L464, Copyright © 1995 by American Physiological Society
Basic fibroblast growth factor and growth factor receptor gene expression in 85% O2-exposed rat lung
S. Buch, R. N. Han, J. Liu, A. Moore, J. D. Edelson, B. A. Freeman, M. Post and A. K. Tanswell
Medical Research Council Group in Lung Development, Hospital for Sick Children Research Institute, Toronto, Canada.
Lungs exposed to elevated O2 concentrations suffer an initial loss of type
I pneumocytes, followed by a reparative type II pneumocyte hyperplasia. We
hypothesized that type II pneumocyte hyperplasia after exposure of young
adult rats to 85% O2 in vivo would be temporally related to 1) an increased
concentration of intrapulmonary basic fibroblast growth factor (bFGF), a
potent stimulator of type II pneumocyte DNA synthesis in vitro, and 2) an
upregulation of pneumocyte receptors for bFGF (FGF-R). Increased rat lung
bFGF mRNA, relative to air-exposed control animals, was observed at 4 days
of exposure, with no increase at days 6 and 14 of exposure. Parallel
changes were observed with bFGF receptor (flg) mRNA. Nuclear runoff assays
confirmed increased transcription of both bFGF and flg genes in response to
85% O2, whereas increased translation at 6 days of exposure was confirmed
by protein immunoanalysis. Immunohistochemistry demonstrated a broad
distribution of bFGF throughout the lung, including the alveolar
epithelium, which increased after 6 and 14 days of exposure to 85% O2. Our
findings are compatible with a role for bFGF in O2-mediated pneumocyte
hyperplasia.
