Insulin-like growth factor-I and type I insulin-like growth factor receptor in 85% O2-exposed rat lung.
The expression of insulin-like growth factor I (IGF-I) and insulin-like growth factor II (IGF-II) was studied in the lungs of adult rats exposed to air or 85% O2, using Northern analysis, in situ hybridization, and immunohistochemistry. Distribution of the type I insulin-like growth factor receptor (IGF-IR) was assessed by immunohistochemistry. IGF-I, but not IGF-II, was localized to airway epithelium, while IGF-IR was localized to perivascular and peribronchial cells, in the lungs of animals breathing air. IGF-II mRNA did not increase with exposure to 85% O2, but IGF-II was localized to sites of perivascular edema and to occasional peribronchial cells. A widespread increase in IGF-I mRNA and peptide was seen after both a 6-day and a 14-day exposure to O2, with maximal expression in the airway and alveolar epithelium, and lesser expression in interstitial cells. After 6 days in 85% O2, increased IGF-IR immunoreactivity was localized to both perivascular and peribronchial cells and to endothelial cells. By 14 days in 85% O2, IGF-IR immunoreactivity was also localized to alveolar epithelial cells. The distribution of IGF-IR immunoreactivity was consistent with a paracrine role for IGF-I in O2-mediated pulmonary hypertension and airway hyperreactivity, by mediating smooth muscle cell hyperplasia, as well as a role in endothelial cell repair and late pneumocyte hyperplasia. The relative insensitivity of IGF-IR immunohistochemistry did not allow us to identify cells with low abundance IGF-IR, and potential cellular targets for IGF-I actions after O2-exposure may be even more extensive than those recognized here.
Han
R N
RN
Medical Research Council Group in Lung Development, Hospital for Sick Children Research Institute, University of Toronto, Ontario, Canada.
Han
V K
VK
Buch
S
S
Freeman
B A
BA
Post
M
M
Tanswell
A K
AK
D000818:Animals; D005260:Female; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000378:metabolism*
D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D010100:Oxygen