HYPEROXIA INHIBITS FETAL-RAT LUNG FIBROBLAST PROLIFERATION AND EXPRESSION OF PROCOLLAGENS

The direct effects of hyperoxia on collagen production by fetal lung f ibroblasts are unknown and would be important to the understanding of the molecular mechanisms involved in bronchopulmonary dysplasia in pre mature 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. Fibrobla sts from 19-day-old rat fetuses (term is 22 days) were obtained. Test plates were incubated in hyperoxia and controls in room air for varyin g time periods. Cell viability in both conditions was >97% as determin ed by trypan blue exclusion. Fibroblast proliferation in nonconfluent cultures was found to be significantly reduced with exposure to hypero xia (P < 0.001). Steady-state levels of type I and III procollagen mRN As, analyzed on Northern blots hybridized to [P-32]cDNA probes, were s ignificantly decreased in hyperoxia (P < 0.01). This effect was noted as early as 4 h of exposure to hyperoxia and persisted for 5 days. The re was a significant inverse correlation between duration of exposure to Oz and steady-state levels of mRNA for alpha(1)(I)-procollagen (r = -0.904) and alpha(1)(III)-procollagen (r = -0.971). There were no sig nificant changes in steady-state levels of p-actin mRNA. We also found a significant decrease in collagen synthesis in hyperoxia-exposed fib roblasts (P < 0.05). We conclude that hyperoxia directly effects a red uction in fetal lung fibroblast proliferation and net collagen product ion at a pretranslational level.