Endogenous retinoids increase perinatal elastin gene expression in rat lung fibroblasts and fetal explants.
During late gestation, the lungs of rats contain retinyl esters, but their concentration decreases considerably at the time of birth. The regulation of the acquisition and utilization of these stored retinoids remains poorly understood, although it has been hypothesized that they are involved in surfactant production and alveolar septal formation. Previous investigations demonstrated that exogenous retinoic acid increases elastin production in cultured neonatal lung fibroblasts and increases the number of alveoli when it is administered to neonatal rats. It has been hypothesized that these pulmonary stores of retinyl esters may regulate the perinatal expression of various genes in the lung, including elastin. To test this hypothesis, inhibitors of retinoid metabolism were used to reduce the flux of retinyl esters to retinoic acid, and the effects of this maneuver on elastin gene expression were analyzed. Inhibitors of alcohol and aldehyde dehydrogenases and of retinyl ester hydrolases decreased the steady-state level of tropoelastin mRNA without reducing alpha 1(I) procollagen mRNA. The magnitude of the effects of the inhibitors was retinol dependent and was significantly reduced in lung tissue that was obtained from vitamin A-deficient fetuses. These findings suggest that the late gestational pulmonary stores of retinoids may increase elastin gene expression during the fetal and early postnatal life in the rat.
McGowan
S E
SE
Department of Veterans Affairs Research Service, Iowa City 52246, USA.
Doro
M M
MM
Jackson
S K
SK
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002478:Cells, Cultured; D004549:Elastin / Q000235:genetics*; D005333:Fetus / Q000166:cytology / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012176:Retinoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014333:Tropoelastin / Q000235:genetics; D014801:Vitamin A / Q000037:antagonists & inhibitors / Q000378:metabolism
D012333:RNA, Messenger; D012176:Retinoids; D014333:Tropoelastin; D014801:Vitamin A; D004549:Elastin