Effect of Hyperoxia on Retinoid Metabolism and Retinoid Receptor Expression in the Lungs of Newborn Mice.
BACKGROUND
Preterm newborns that receive oxygen therapy often develop bronchopulmonary dysplasia (BPD), which is abnormal lung development characterized by impaired alveologenesis. Oxygen-mediated injury is thought to disrupt normal lung growth and development. However, the mechanism of hyperoxia-induced BPD has not been extensively investigated. We established a neonatal mouse model to investigate the effects of normobaric hyperoxia on retinoid metabolism and retinoid receptor expression.


METHODS
Newborn mice were exposed to hyperoxic or normoxic conditions for 15 days. The concentration of retinol and retinyl palmitate in the lung was measured by HPLC to gauge retinoid metabolism. Retinoid receptor mRNA levels were assessed by real-time PCR. Proliferation and retinoid receptor expression in A549 cells were assessed in the presence and absence of exogenous vitamin A.


RESULTS
Hyperoxia significantly reduced the body and lung weight of neonatal mice. Hyperoxia also downregulated expression of RARα, RARγ, and RXRγ in the lungs of neonatal mice. In vitro, hyperoxia inhibited proliferation and expression of retinoid receptors in A549 cells.


CONCLUSIONS
Hyperoxia disrupted retinoid receptor expression in neonatal mice.
Graduate Institute of Clinical Medicine College of Medicine of National Taiwan University, Taipei, Taiwan.
Hsing-Jin
HJ
Chen
Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan.
Bor-Luen
BL
Chiang
D000818:Animals; D000831:Animals, Newborn; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008813:Mice, Inbred ICR; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism*; D000084562:Retinyl Esters; D016019:Survival Analysis; D013936:Thymidine / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D004224:Diterpenes; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D013936:Thymidine