POSTNATAL AGE AT ONSET OF HYPEROXIC EXPOSURE INFLUENCES DEVELOPMENTALLY-REGULATED TROPOELASTIN GENE-EXPRESSION IN THE NEONATAL RAT LUNG

Upregulation of tropoelastin (TE) gene expression in rat lung intersti tial fibroblasts normally occurs during alveolar septation. TE message increases at the end of the first week of life, peaks on days 9-11, a nd returns to barely detectable levels over the next 7-10 days. Our pr evious in situ hybridization studies indicated that exposure of pups t o > 95% oxygen from 3 to 13 days of age interfered with the increase i n TE gene expression in interstitial fibroblasts normally seen during septation. However, when the pups were returned to room air, lung fibr oblast TE message levels increased, exceeding levels seen in control l ungs during the exposure. In addition, TE message levels remained elev ated for a week after levels in control lungs had returned to backgrou nd. A possible interpretation of these results was that the developmen tally regulated increase in TE messenger RNA (mRNA) was downregulated by the hyperoxic exposure but resumed when the pups were returned to a normoxic environment. We report herein the results of a subsequent st udy conducted to determine whether continued hyperoxic exposure beyond day 13 would further delay the peak in TE mRNA. Rat pups were exposed to 95% O-2 from 5 to 17 days of age. TE and glyceraldehyde-3-phosphat e dehydrogenase (GAPDH) message levels in lung interstitial fibroblast s were assessed by in situ hybridization. As observed in pups exposed from 3 to 13 days, hyperoxic exposure from days 5 to 17 also extended the period during which TE mRNA levels were elevated. After exposure, TE message levels were 99%, 262%, and 223% of controls on days 19, 21, and 23 respectively. In addition, delaying the exposure 2 days until the pups were 5 days old resulted in an upregulation of TE message, re lative to control values, during the hyperoxic exposure. In hyperoxic pups, values for TE message expression were 105%, 152%, 168%, and 144% of control pups on days 9, 11, 13, and 16 respectively. The influence on peak TE message expression of postnatal age at the time of exposur e was further explored to verify the results of the 3-13 and 5-17 day exposures. When pups were exposed continuously from 2, 3, 4, 5, or 6 d ays until 11 days of age, the results of both in situ hybridization an d Northern blot analysis confirmed our previous observations, demonstr ating that the postnatal age at which hyperoxic exposure is initiated influences TE message expression in the developing lung.