Extracellular Signal-Regulated Kinase 1 Alone Is Dispensable for Hyperoxia-Mediated Alveolar and Pulmonary Vascular Simplification in Neonatal Mice
Bronchopulmonary dysplasia (BPD) is a morbid lung disease distinguished by lung alveolar and vascular simplification. Hyperoxia, an important BPD causative factor, increases extracellular signal-regulated kinases (ERK)-1/2 expression, whereas decreased lung endothelial cell <i>ERK2</i> e...
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MDPI AG
2022-06-01
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author | Renuka T. Menon Shyam Thapa Amrit Kumar Shrestha Roberto Barrios Binoy Shivanna |
author_facet | Renuka T. Menon Shyam Thapa Amrit Kumar Shrestha Roberto Barrios Binoy Shivanna |
author_sort | Renuka T. Menon |
collection | DOAJ |
description | Bronchopulmonary dysplasia (BPD) is a morbid lung disease distinguished by lung alveolar and vascular simplification. Hyperoxia, an important BPD causative factor, increases extracellular signal-regulated kinases (ERK)-1/2 expression, whereas decreased lung endothelial cell <i>ERK2</i> expression reduces angiogenesis and potentiates hyperoxia-mediated BPD in mice. However, ERK1′s role in experimental BPD is unclear. Thus, we hypothesized that hyperoxia-induced experimental BPD would be more severe in global <i>ERK1</i>-knockout (<i>ERK1</i><sup>-/-</sup>) mice than their wild-type (<i>ERK1</i><sup>+/+</sup> mice) littermates. We determined the extent of lung development, ERK1/2 expression, inflammation, and oxidative stress in <i>ERK1</i><sup>-/-</sup> and <i>ERK1</i><sup>+/+</sup> mice exposed to normoxia (FiO<sub>2</sub> 21%) or hyperoxia (FiO<sub>2</sub> 70%). We also quantified the extent of angiogenesis and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) production in hyperoxia-exposed neonatal human pulmonary microvascular endothelial cells (HPMECs) with normal and decreased <i>ERK1</i> signaling. Compared with <i>ERK1</i><sup>+/+</sup> mice, <i>ERK1</i><sup>-/-</sup> mice displayed increased pulmonary ERK2 activation upon hyperoxia exposure. However, the extent of hyperoxia-induced inflammation, oxidative stress, and interrupted lung development was similar in <i>ERK1</i><sup>-/-</sup> and <i>ERK1</i><sup>+/+</sup> mice. <i>ERK1</i> knockdown in HPMECs increased ERK2 activation at baseline, but did not affect in vitro angiogenesis and hyperoxia-induced H<sub>2</sub>O<sub>2</sub> production. Thus, we conclude <i>ERK1</i> is dispensable for hyperoxia-induced experimental BPD due to compensatory ERK2 activation. |
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spelling | doaj.art-e2aa94f69536467186ec474298a0db7f2023-11-23T15:20:06ZengMDPI AGAntioxidants2076-39212022-06-01116113010.3390/antiox11061130Extracellular Signal-Regulated Kinase 1 Alone Is Dispensable for Hyperoxia-Mediated Alveolar and Pulmonary Vascular Simplification in Neonatal MiceRenuka T. Menon0Shyam Thapa1Amrit Kumar Shrestha2Roberto Barrios3Binoy Shivanna4Section of Neonatology, Department of Pediatrics, Baylor College of Medicine (BCM), Houston, TX 77030, USASection of Neonatology, Department of Pediatrics, Baylor College of Medicine (BCM), Houston, TX 77030, USASection of Neonatology, Department of Pediatrics, Baylor College of Medicine (BCM), Houston, TX 77030, USADepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USASection of Neonatology, Department of Pediatrics, Baylor College of Medicine (BCM), Houston, TX 77030, USABronchopulmonary dysplasia (BPD) is a morbid lung disease distinguished by lung alveolar and vascular simplification. Hyperoxia, an important BPD causative factor, increases extracellular signal-regulated kinases (ERK)-1/2 expression, whereas decreased lung endothelial cell <i>ERK2</i> expression reduces angiogenesis and potentiates hyperoxia-mediated BPD in mice. However, ERK1′s role in experimental BPD is unclear. Thus, we hypothesized that hyperoxia-induced experimental BPD would be more severe in global <i>ERK1</i>-knockout (<i>ERK1</i><sup>-/-</sup>) mice than their wild-type (<i>ERK1</i><sup>+/+</sup> mice) littermates. We determined the extent of lung development, ERK1/2 expression, inflammation, and oxidative stress in <i>ERK1</i><sup>-/-</sup> and <i>ERK1</i><sup>+/+</sup> mice exposed to normoxia (FiO<sub>2</sub> 21%) or hyperoxia (FiO<sub>2</sub> 70%). We also quantified the extent of angiogenesis and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) production in hyperoxia-exposed neonatal human pulmonary microvascular endothelial cells (HPMECs) with normal and decreased <i>ERK1</i> signaling. Compared with <i>ERK1</i><sup>+/+</sup> mice, <i>ERK1</i><sup>-/-</sup> mice displayed increased pulmonary ERK2 activation upon hyperoxia exposure. However, the extent of hyperoxia-induced inflammation, oxidative stress, and interrupted lung development was similar in <i>ERK1</i><sup>-/-</sup> and <i>ERK1</i><sup>+/+</sup> mice. <i>ERK1</i> knockdown in HPMECs increased ERK2 activation at baseline, but did not affect in vitro angiogenesis and hyperoxia-induced H<sub>2</sub>O<sub>2</sub> production. Thus, we conclude <i>ERK1</i> is dispensable for hyperoxia-induced experimental BPD due to compensatory ERK2 activation.https://www.mdpi.com/2076-3921/11/6/1130extracellular signal-regulated kinases 1 and 2neonatal HPMECshydrogen peroxidehyperoxiabronchopulmonary dysplasia |
spellingShingle | Renuka T. Menon Shyam Thapa Amrit Kumar Shrestha Roberto Barrios Binoy Shivanna Extracellular Signal-Regulated Kinase 1 Alone Is Dispensable for Hyperoxia-Mediated Alveolar and Pulmonary Vascular Simplification in Neonatal Mice Antioxidants extracellular signal-regulated kinases 1 and 2 neonatal HPMECs hydrogen peroxide hyperoxia bronchopulmonary dysplasia |
title | Extracellular Signal-Regulated Kinase 1 Alone Is Dispensable for Hyperoxia-Mediated Alveolar and Pulmonary Vascular Simplification in Neonatal Mice |
title_full | Extracellular Signal-Regulated Kinase 1 Alone Is Dispensable for Hyperoxia-Mediated Alveolar and Pulmonary Vascular Simplification in Neonatal Mice |
title_fullStr | Extracellular Signal-Regulated Kinase 1 Alone Is Dispensable for Hyperoxia-Mediated Alveolar and Pulmonary Vascular Simplification in Neonatal Mice |
title_full_unstemmed | Extracellular Signal-Regulated Kinase 1 Alone Is Dispensable for Hyperoxia-Mediated Alveolar and Pulmonary Vascular Simplification in Neonatal Mice |
title_short | Extracellular Signal-Regulated Kinase 1 Alone Is Dispensable for Hyperoxia-Mediated Alveolar and Pulmonary Vascular Simplification in Neonatal Mice |
title_sort | extracellular signal regulated kinase 1 alone is dispensable for hyperoxia mediated alveolar and pulmonary vascular simplification in neonatal mice |
topic | extracellular signal-regulated kinases 1 and 2 neonatal HPMECs hydrogen peroxide hyperoxia bronchopulmonary dysplasia |
url | https://www.mdpi.com/2076-3921/11/6/1130 |
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