AJP - Lung Cellular and Molecular Physiology, Vol 273, Issue 4 726-L732, Copyright © 1997 by American Physiological Society
Hyperoxia inhibits fetal rat lung fibroblast proliferation and expression of procollagens
N. Hussain, F. Wu, C. Christian and M. J. Kresch
Department of Pediatrics, University of Connecticut School of Medicine, Farmington 06030-2203, USA.
The direct effects of hyperoxia on collagen production by fetal lung
fibroblasts are unknown and would be important to the understanding of the
molecular mechanisms involved in bronchopulmonary dysplasia in premature
infants. We studied the effect of hyperoxia on 1) proliferation, 2) mRNA
levels for type I and III procollagens, and 3) net collagen production in
primary cultures of fetal rat lung fibroblasts. Fibroblasts from 19-day-old
rat fetuses (term is 22 days) were obtained. Test plates were incubated in
hyperoxia and controls in room air for varying time periods. Cell viability
in both conditions was >97% as determined by trypan blue exclusion.
Fibroblast proliferation in nonconfluent cultures was found to be
significantly reduced with exposure to hyperoxia (P < 0.001).
Steady-state levels of type I and III procollagen mRNAs, analyzed on
Northern blots hybridized to [32P]cDNA probes, were significantly decreased
in hyperoxia (P < 0.01). This effect was noted as early as 4 h of
exposure to hyperoxia and persisted for 5 days. There was a significant
inverse correlation between duration of exposure to O2 and steady-state
levels of mRNA for alpha1(I)-procollagen (r = -0.904) and
alpha1(III)-procollagen (r = -0.971). There were no significant changes in
steady-state levels of beta-actin mRNA. We also found a significant
decrease in collagen synthesis in hyperoxia-exposed fibroblasts (P <
0.05). We conclude that hyperoxia directly effects a reduction in fetal
lung fibroblast proliferation and net collagen production at a
pretranslational level.
