Thyroid hormone modulates hyperoxic neonatal lung injury and mitochondrial function

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

doi: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

Published March 14, 2023 - More info

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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.

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

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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

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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