Insulin-like growth factor-i and the type i insulin-like growth
factor receptor in 85% o2-exposed rat lung.
Han, Robin N. N., Victor K. M. Han, Shilpa Buch, Bruce A. Freeman,
Martin Post, and A. Keith Tanswell.
Medical Research Council Group in Lung Development (SB, RNNH, MP
& AKT), Hospital for Sick Children Research Institute and
Department of Paediatrics, University of Toronto, Toronto, Ontario,
Canada M5G 1X8; Medical Research Council Group in Fetal and Neonatal
Health and Development (VKMH), Lawson Research Institute, St.
Joseph's Health Centre and Department of Paediatrics, University of
Western Ontario, London, Ontario, Canada N6A 4V2; and Departments of
Anesthesiology, Biochemistry and Pediatrics (BAF), University of
Alabama at Birmingham, Birmingham, Alabama 35294
APStracts 3:0039L, 1996.
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 oedema and to occasional
peribronchial cells. A widespread increase in IGF-I mRNA and peptide
was seen after both a 6-d and a 14-d exposure to O2, with maximal
expression in the airway and alveolar epithelium, and lesser
expression in interstitial cells. After 6 d in 85% O2, increased IGF
-IR immunoreactivity was localized to both perivascular and
peribronchial cells and to endothelial cells. By 14 d 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,
following O2-exposure, may be even more extensive than those
recognized here.
Received 13 October 1995; accepted in final form 6 March 1996.
APS Manuscript Number L303-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96