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Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice
Inflammation causes bronchopulmonary dysplasia (BPD), a common lung disease of preterm infants. One reason this disease lacks specific therapies is the paucity of information on the mechanisms regulating inflammation in developing lungs. We address this gap by characterizing the lymphatic phenotype...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045755/ https://www.ncbi.nlm.nih.gov/pubmed/36978868 http://dx.doi.org/10.3390/antiox12030620 |
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author | Shankar, Nithyapriya Thapa, Shyam Shrestha, Amrit Kumar Sarkar, Poonam Gaber, M. Waleed Barrios, Roberto Shivanna, Binoy |
author_facet | Shankar, Nithyapriya Thapa, Shyam Shrestha, Amrit Kumar Sarkar, Poonam Gaber, M. Waleed Barrios, Roberto Shivanna, Binoy |
author_sort | Shankar, Nithyapriya |
collection | PubMed |
description | Inflammation causes bronchopulmonary dysplasia (BPD), a common lung disease of preterm infants. One reason this disease lacks specific therapies is the paucity of information on the mechanisms regulating inflammation in developing lungs. We address this gap by characterizing the lymphatic phenotype in an experimental BPD model because lymphatics are major regulators of immune homeostasis. We hypothesized that hyperoxia (HO), a major risk factor for experimental and human BPD, disrupts lymphatic endothelial homeostasis using neonatal mice and human dermal lymphatic endothelial cells (HDLECs). Exposure to 70% O(2) for 24–72 h decreased the expression of prospero homeobox 1 (Prox1) and vascular endothelial growth factor c (Vegf-c) and increased the expression of heme oxygenase 1 and NAD(P)H dehydrogenase [quinone]1 in HDLECs, and reduced their tubule formation ability. Next, we determined Prox1 and Vegf-c mRNA levels on postnatal days (P) 7 and 14 in neonatal murine lungs. The mRNA levels of these genes increased from P7 to P14, and 70% O(2) exposure for 14 d (HO) attenuated this physiological increase in pro-lymphatic factors. Further, HO exposure decreased VEGFR3(+) and podoplanin(+) lymphatic vessel density and lymphatic function in neonatal murine lungs. Collectively, our results validate the hypothesis that HO disrupts lymphatic endothelial homeostasis. |
format | Online Article Text |
id | pubmed-10045755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100457552023-03-29 Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice Shankar, Nithyapriya Thapa, Shyam Shrestha, Amrit Kumar Sarkar, Poonam Gaber, M. Waleed Barrios, Roberto Shivanna, Binoy Antioxidants (Basel) Article Inflammation causes bronchopulmonary dysplasia (BPD), a common lung disease of preterm infants. One reason this disease lacks specific therapies is the paucity of information on the mechanisms regulating inflammation in developing lungs. We address this gap by characterizing the lymphatic phenotype in an experimental BPD model because lymphatics are major regulators of immune homeostasis. We hypothesized that hyperoxia (HO), a major risk factor for experimental and human BPD, disrupts lymphatic endothelial homeostasis using neonatal mice and human dermal lymphatic endothelial cells (HDLECs). Exposure to 70% O(2) for 24–72 h decreased the expression of prospero homeobox 1 (Prox1) and vascular endothelial growth factor c (Vegf-c) and increased the expression of heme oxygenase 1 and NAD(P)H dehydrogenase [quinone]1 in HDLECs, and reduced their tubule formation ability. Next, we determined Prox1 and Vegf-c mRNA levels on postnatal days (P) 7 and 14 in neonatal murine lungs. The mRNA levels of these genes increased from P7 to P14, and 70% O(2) exposure for 14 d (HO) attenuated this physiological increase in pro-lymphatic factors. Further, HO exposure decreased VEGFR3(+) and podoplanin(+) lymphatic vessel density and lymphatic function in neonatal murine lungs. Collectively, our results validate the hypothesis that HO disrupts lymphatic endothelial homeostasis. MDPI 2023-03-02 /pmc/articles/PMC10045755/ /pubmed/36978868 http://dx.doi.org/10.3390/antiox12030620 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shankar, Nithyapriya Thapa, Shyam Shrestha, Amrit Kumar Sarkar, Poonam Gaber, M. Waleed Barrios, Roberto Shivanna, Binoy Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice |
title | Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice |
title_full | Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice |
title_fullStr | Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice |
title_full_unstemmed | Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice |
title_short | Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice |
title_sort | hyperoxia disrupts lung lymphatic homeostasis in neonatal mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045755/ https://www.ncbi.nlm.nih.gov/pubmed/36978868 http://dx.doi.org/10.3390/antiox12030620 |
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