Am. J. Respir. Cell Mol. Biol., Vol 14, No. 2, Feb 1996, 177-185.
Postnatal age at onset of hyperoxic exposure influences developmentally regulated tropoelastin gene expression in the neonatal rat lung
MC Bruce, C Honaker and P Karathanasis
Department of Pediatrics, University of Kentucky, Lexington 40536, USA.
Upregulation of tropoelastin (TE) gene expression in rat lung interstitial
fibroblasts normally occurs during alveolar septation. TE message increases
at the end of the first week of life, peaks on days 9- 11, and returns to
barely detectable levels over the next 7-10 days. Our previous in situ
hybridization studies indicated that exposure of pups to > 95% oxygen
from 3 to 13 days of age interfered with the increased in TE gene
expression in interstitial fibroblasts normally seen during septation.
However, when the pups were returned to room air, lung fibroblast TE
message levels increased, exceeding levels seen in control lungs during the
exposure. In addition, TE message levels remained elevated for a week after
levels in control lungs had returned to background. A possible
interpretation of these results was that the developmentally 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 study conducted to determine
whether continued hyperoxic exposure beyond day 13 would further delay the
peak in TE mRNA. Rat pups were exposed to 95% O2 from 5 to 17 days of age.
TE and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) message levels in
lung interstitial fibroblasts 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,
relative 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 exposure 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 days until 11 days of
age, the results of both in situ hybridization and Northern blot analysis
confirmed our previous observations, demonstrating that the postnatal age
at which hyperoxic exposure is initiated influences TE message expression
in the developing lung.
