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Open Access | 10.1172/jci.insight.160697
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
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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
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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
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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
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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
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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
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Kaminski, N.
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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
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Ambalavanan, N.
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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
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Published March 14, 2023 - More info
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.