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ResearchIn-Press PreviewPulmonology Open Access | 10.1172/jci.insight.160697

Thyroid hormone modulates hyperoxic neonatal lung injury and mitochondrial function

Bianca M. Vamesu,1 Teodora Nicola,1 Rui Li,1 Snehashis Hazra,1 Sadis Matalon,2 Naftali Kaminski,3 Namasivayam Ambalavanan,4 and Jegen Kandasamy1

1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, United States of America

2Department of Anesthesiology and Perioperative Medicine, The University of Alabama at Birmingham, Birmingham, United States of America

3Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, United States of America

4Neonatology, The University of Alabama at Birmingham, Birmingham, United States of America

Find articles by Vamesu, B. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, United States of America

2Department of Anesthesiology and Perioperative Medicine, The University of Alabama at Birmingham, Birmingham, United States of America

3Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, United States of America

4Neonatology, The University of Alabama at Birmingham, Birmingham, United States of America

Find articles by Nicola, T. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, United States of America

2Department of Anesthesiology and Perioperative Medicine, The University of Alabama at Birmingham, Birmingham, United States of America

3Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, United States of America

4Neonatology, The University of Alabama at Birmingham, Birmingham, United States of America

Find articles by Li, R. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, United States of America

2Department of Anesthesiology and Perioperative Medicine, The University of Alabama at Birmingham, Birmingham, United States of America

3Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, United States of America

4Neonatology, The University of Alabama at Birmingham, Birmingham, United States of America

Find articles by Hazra, S. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, United States of America

2Department of Anesthesiology and Perioperative Medicine, The University of Alabama at Birmingham, Birmingham, United States of America

3Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, United States of America

4Neonatology, The University of Alabama at Birmingham, Birmingham, United States of America

Find articles by Matalon, S. in: JCI | PubMed | Google Scholar |

1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, United States of America

2Department of Anesthesiology and Perioperative Medicine, The University of Alabama at Birmingham, Birmingham, United States of America

3Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, United States of America

4Neonatology, The University of Alabama at Birmingham, Birmingham, United States of America

Find articles by Kaminski, N. in: JCI | PubMed | Google Scholar |

1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, United States of America

2Department of Anesthesiology and Perioperative Medicine, The University of Alabama at Birmingham, Birmingham, United States of America

3Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, United States of America

4Neonatology, The University of Alabama at Birmingham, Birmingham, United States of America

Find articles by Ambalavanan, N. in: JCI | PubMed | Google Scholar |

1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, United States of America

2Department of Anesthesiology and Perioperative Medicine, The University of Alabama at Birmingham, Birmingham, United States of America

3Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, United States of America

4Neonatology, The University of Alabama at Birmingham, Birmingham, United States of America

Find articles by Kandasamy, J. in: JCI | PubMed | Google Scholar

Published March 14, 2023 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.160697.
Copyright © 2023, Vamesu et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published March 14, 2023 - Version history
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Abstract

Mitochondrial dysfunction at birth predicts bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants. Recently, nebulized thyroid hormone (TH), given as triiodothyronine (T3) was noted to decrease pulmonary fibrosis in adult animals through improved mitochondrial function. We hypothesized that TH may have similar effects on hyperoxia-induced neonatal lung injury and mitochondrial dysfunction. To determine whether intranasal T3 decreases neonatal hyperoxic lung injury in newborn mice, T3 improves mitochondrial function in lung homogenates, neonatal murine lung fibroblasts (NMLF) and umbilical cord-derived mesenchymal stem cells (MSCs) obtained from ELBW infants, and whether neonatal hypothyroxinemia is associated with BPD in ELBW infants. Inhaled T3 (given intranasally) attenuated hyperoxia-induced lung injury and mitochondrial dysfunction in newborn mice. T3 also reduced bioenergetic deficits in UC-MSCs obtained both from infants with no/mild BPD and those with moderate/severe BPD. T3 also increased PGC1α content in lung homogenates of mice exposed to hyperoxia as well as mitochondrial potential in both NMLF and UC-MSCs. ELBW infants who died or developed moderate/severe BPD had lower TT4 compared to survivors with no/mild BPD. TH signaling and function may play a critical role in neonatal lung injury and inhaled T3 supplementation may be useful as a therapeutic strategy for BPD.

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