Retinoids, retinoic acid receptors, and cytoplasmic retinoid
binding proteins in perinatal rat lung fibroblasts.
McGowan, Stephen E., Catherine S. Harvey, and Sheila K. Jackson.
Department of Veterans Affairs Research Service and University of
Iowa College of Medicine, Iowa City, Iowa
APStracts 2:0072L, 1995.
The early postnatal life of most mammals, marks a period of extensive
enlargement of the alveolar surface area and increase in the elastin
content of the lung. The factors which regulate the onset and
abatement of this burst of elastin synthesis have not been
identified. Previous studies of lipid laden rat pulmonary
interstitial fibroblasts (LIF) have shown that their elastin
synthesis is increased in vitro by retinoic acid (RA). We
hypothesized that temporal changes in the endogenous RA content of
LIF may correlate with changes in elastin synthesis by these cells.
LIF were isolated from the lungs of rats at gestational day 19 and
postnatal days 2, 4, 8, and 12 and their retinoid contents were
quantitated. Retinyl esters were highest at gestational day 19 (2.9
0.6 pmol per 106 cells, mean SEM) and decreased to 1.6 0.2 pmol by
postnatal day 2 (p<0.05). This decrease in retinyl esters was
accompanied by an increase in retinol from 0.4 0.1 to 2.0 0.6 pmol
per 106 cells (p<0.05). Retinoic acid increased in LIF from 0.07
0.04 pmol per 106 cells at gestational day 19 to 0.29 0.05 pmol per
106 cells at postnatal day 2 (p<0.05) and increased in whole lung
tissue from 0.07 0.04 to 0.29 0.05 nmol per g, over the same
interval. The increase in RA content was accompanied by an increase
in retinoic acid receptor (RAR) beta and gamma mRNAs. The steady
-state mRNA level of cellular retinol binding protein (CRBP) was high
in LIF, relative to whole lung tissue at day 2. Cellular retinoic
acid binding protein (CRABP) mRNA rose 4 fold from day 2 to day 8 and
then fell by day 12. In summary, RA, RAR, and CRBP mRNA in LIF are
highest prior to the period of maximal elastin synthesis which occurs
at postnatal days 8 and 12. These findings are consistent with the
hyothesis that endogenous RA could contribute to the postnatal
increase in elastin production by pulmonary fibroblasts.
Received 9 January 1995; accepted in final form 25 April 1995.
APS Manuscript Number L6-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 9 May 1995.