Basic fibroblast growth factor and growth factor receptor gene expression in 85% O2-exposed rat lung.
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.
Buch
S
S
Medical Research Council Group in Lung Development, Hospital for Sick Children Research Institute, Toronto, Canada.
Han
R N
RN
Liu
J
J
Moore
A
A
Edelson
J D
JD
Freeman
B A
BA
Post
M
M
Tanswell
A K
AK
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D010100:Oxygen