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Thyroid hormone modulates hyperoxic neonatal lung injury and mitochondrial function
Bianca M. Vamesu, … , Namasivayam Ambalavanan, Jegen Kandasamy
Bianca M. Vamesu, … , Namasivayam Ambalavanan, Jegen Kandasamy
Published March 14, 2023
Citation Information: JCI Insight. 2023;8(8):e160697. https://doi.org/10.1172/jci.insight.160697.
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Research Article Pulmonology

Thyroid hormone modulates hyperoxic neonatal lung injury and mitochondrial function

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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. In this study, we tested the hypothesis that TH may have similar effects on hyperoxia-induced neonatal lung injury and mitochondrial dysfunction by testing whether i.n. T3 decreases neonatal hyperoxic lung injury in newborn mice; whether T3 improves mitochondrial function in lung homogenates, neonatal murine lung fibroblasts (NMLFs), and umbilical cord–derived mesenchymal stem cells (UC-MSCs) obtained from ELBW infants; and whether neonatal hypothyroxinemia is associated with BPD in ELBW infants. We found that inhaled T3 (given i.n.) attenuated hyperoxia-induced lung injury and mitochondrial dysfunction in newborn mice. T3 also reduced bioenergetic deficits in UC-MSCs obtained from both infants with no or mild BPD and those with moderate to severe BPD. T3 also increased the content of peroxisome proliferator–activated receptor γ coactivator 1α in lung homogenates of mice exposed to hyperoxia as well as mitochondrial potential in both NMLFs and UC-MSCs. ELBW infants who died or developed moderate to severe BPD had lower total T4 (TT4) compared with survivors with no or mild BPD. In conclusion, 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.

Authors

Bianca M. Vamesu, Teodora Nicola, Rui Li, Snehashis Hazra, Sadis Matalon, Naftali Kaminski, Namasivayam Ambalavanan, Jegen Kandasamy

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Figure 3

Bioenergetic function and electron transport chain complex activities of lung mitochondria.

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Bioenergetic function and electron transport chain complex activities of...
A total of 300 μg mitochondria per sample isolated from lung homogenates of 14-day-old mice that received vehicle (normal saline) or T3 while being exposed to air or hyperoxia used to measure OCR in the presence of various substrates and mitochondrial effectors. (A) Basal OCR. (B) Maximal OCR. (C) ATP-linked OCR. (D) RCR, which is a measure of mitochondrial oxidative phosphorylation efficiency. (E) Complex IV (C-IV) activity. N = minimum of 6 mice/group. All data were analyzed by 2-way ANOVA or Kruskal-Wallis tests, followed by post hoc analyses. Box represents median/IQR; whiskers represent maximum and minimum values. *P < 0.05; **P < 0.005. NS, normal saline.

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