RESEARCH ARTICLE
Effect of Hyperoxia on Retinoid Metabolism and Retinoid Receptor Expression in the Lungs of Newborn Mice Hsing-Jin Chen1, Bor-Luen Chiang2* 1 Graduate Institute of Clinical Medicine College of Medicine of National Taiwan University, Taipei, Taiwan, 2 Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan * [email protected]
Abstract 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. OPEN ACCESS Citation: Chen H-J, Chiang B-L (2015) Effect of Hyperoxia on Retinoid Metabolism and Retinoid Receptor Expression in the Lungs of Newborn Mice. PLoS ONE 10(10): e0140343. doi:10.1371/journal. pone.0140343 Editor: Lynn M Schnapp, Medical University of South Carolina, UNITED STATES Received: September 12, 2014 Accepted: September 24, 2015 Published: October 28, 2015 Copyright: © 2015 Chen, Chiang. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Conclusion Hyperoxia disrupted retinoid receptor expression in neonatal mice.
Data Availability Statement: All relevant data are within the paper. Funding: The authors have no support or funding to report.
Introduction
Competing Interests: The authors have declared that no competing interests exist.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that often develops in premature infants who require mechanical ventilation with oxygen [1]. The pathophysiological changes of
PLOS ONE | DOI:10.1371/journal.pone.0140343 October 28, 2015
1 / 14
Hyperoxia Alters Retinoid Metabolism and Retinoid Receptor Expression
BPD include inflammation, airway fibrosis, and smooth muscle hypertrophy, which can result in poor alveolarization and disrupted microvascular development [2]. Almost one-quarter of extremely low birth weight infants (
Effect of Hyperoxia on Retinoid Metabolism and Retinoid Receptor Expression in the Lungs of Newborn Mice Hsing-Jin Chen1, Bor-Luen Chiang2* 1 Graduate Institute of Clinical Medicine College of Medicine of National Taiwan University, Taipei, Taiwan, 2 Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan * [email protected]
Abstract 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. OPEN ACCESS Citation: Chen H-J, Chiang B-L (2015) Effect of Hyperoxia on Retinoid Metabolism and Retinoid Receptor Expression in the Lungs of Newborn Mice. PLoS ONE 10(10): e0140343. doi:10.1371/journal. pone.0140343 Editor: Lynn M Schnapp, Medical University of South Carolina, UNITED STATES Received: September 12, 2014 Accepted: September 24, 2015 Published: October 28, 2015 Copyright: © 2015 Chen, Chiang. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Conclusion Hyperoxia disrupted retinoid receptor expression in neonatal mice.
Data Availability Statement: All relevant data are within the paper. Funding: The authors have no support or funding to report.
Introduction
Competing Interests: The authors have declared that no competing interests exist.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that often develops in premature infants who require mechanical ventilation with oxygen [1]. The pathophysiological changes of
PLOS ONE | DOI:10.1371/journal.pone.0140343 October 28, 2015
1 / 14
Hyperoxia Alters Retinoid Metabolism and Retinoid Receptor Expression
BPD include inflammation, airway fibrosis, and smooth muscle hypertrophy, which can result in poor alveolarization and disrupted microvascular development [2]. Almost one-quarter of extremely low birth weight infants (
