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Hypoxia-Induced miR-15a Promotes Mesenchymal Ablation and Adaptation to Hypoxia during Lung Development in Chicken

The lungs undergo changes that are adaptive for high elevation in certain animal species. In chickens, animals bred at high elevations (e.g., Tibet chickens) are better able to hatch and survive under high-altitude conditions. In addition, lowland chicken breeds undergo physiological effects and suf...

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Autores principales: Hao, Rui, Hu, Xiaoxiang, Wu, Changxin, Li, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041788/
https://www.ncbi.nlm.nih.gov/pubmed/24887070
http://dx.doi.org/10.1371/journal.pone.0098868
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author Hao, Rui
Hu, Xiaoxiang
Wu, Changxin
Li, Ning
author_facet Hao, Rui
Hu, Xiaoxiang
Wu, Changxin
Li, Ning
author_sort Hao, Rui
collection PubMed
description The lungs undergo changes that are adaptive for high elevation in certain animal species. In chickens, animals bred at high elevations (e.g., Tibet chickens) are better able to hatch and survive under high-altitude conditions. In addition, lowland chicken breeds undergo physiological effects and suffer greater mortality when they are exposed to hypoxic conditions during embryonic development. Although these physiological effects have been noted, the mechanisms that are responsible for hypoxia-induced changes in lung development and function are not known. Here we have examined the role of a particular microRNA (miRNA) in the regulation of lung development under hypoxic conditions. When chicks were incubated in low oxygen (hypoxia), miR-15a was significantly increased in embryonic lung tissue. The expression level of miR-15a in hypoxic Tibet chicken embryos increased and remained relatively high at embryonic day (E)16–20, whereas in normal chickens, expression increased and peaked at E19–20, at which time the cross-current gas exchange system (CCGS) is developing. Bcl-2 was a translationally repressed target of miR-15a in these chickens. miR-16, a cluster and family member of miR-15a, was detected but did not participate in the posttranscriptional regulation of bcl-2. Around E19, the hypoxia-induced decrease in Bcl-2 protein resulted in apoptosis in the mesenchyme around the migrating tubes, which led to an expansion and migration of the tubes that would become the air capillary network and the CCGS. Thus, interfering with miR-15a expression in lung tissue may be a novel therapeutic strategy for hypoxia insults and altitude adaptation.
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spelling pubmed-40417882014-06-09 Hypoxia-Induced miR-15a Promotes Mesenchymal Ablation and Adaptation to Hypoxia during Lung Development in Chicken Hao, Rui Hu, Xiaoxiang Wu, Changxin Li, Ning PLoS One Research Article The lungs undergo changes that are adaptive for high elevation in certain animal species. In chickens, animals bred at high elevations (e.g., Tibet chickens) are better able to hatch and survive under high-altitude conditions. In addition, lowland chicken breeds undergo physiological effects and suffer greater mortality when they are exposed to hypoxic conditions during embryonic development. Although these physiological effects have been noted, the mechanisms that are responsible for hypoxia-induced changes in lung development and function are not known. Here we have examined the role of a particular microRNA (miRNA) in the regulation of lung development under hypoxic conditions. When chicks were incubated in low oxygen (hypoxia), miR-15a was significantly increased in embryonic lung tissue. The expression level of miR-15a in hypoxic Tibet chicken embryos increased and remained relatively high at embryonic day (E)16–20, whereas in normal chickens, expression increased and peaked at E19–20, at which time the cross-current gas exchange system (CCGS) is developing. Bcl-2 was a translationally repressed target of miR-15a in these chickens. miR-16, a cluster and family member of miR-15a, was detected but did not participate in the posttranscriptional regulation of bcl-2. Around E19, the hypoxia-induced decrease in Bcl-2 protein resulted in apoptosis in the mesenchyme around the migrating tubes, which led to an expansion and migration of the tubes that would become the air capillary network and the CCGS. Thus, interfering with miR-15a expression in lung tissue may be a novel therapeutic strategy for hypoxia insults and altitude adaptation. Public Library of Science 2014-06-02 /pmc/articles/PMC4041788/ /pubmed/24887070 http://dx.doi.org/10.1371/journal.pone.0098868 Text en © 2014 Hao et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hao, Rui
Hu, Xiaoxiang
Wu, Changxin
Li, Ning
Hypoxia-Induced miR-15a Promotes Mesenchymal Ablation and Adaptation to Hypoxia during Lung Development in Chicken
title Hypoxia-Induced miR-15a Promotes Mesenchymal Ablation and Adaptation to Hypoxia during Lung Development in Chicken
title_full Hypoxia-Induced miR-15a Promotes Mesenchymal Ablation and Adaptation to Hypoxia during Lung Development in Chicken
title_fullStr Hypoxia-Induced miR-15a Promotes Mesenchymal Ablation and Adaptation to Hypoxia during Lung Development in Chicken
title_full_unstemmed Hypoxia-Induced miR-15a Promotes Mesenchymal Ablation and Adaptation to Hypoxia during Lung Development in Chicken
title_short Hypoxia-Induced miR-15a Promotes Mesenchymal Ablation and Adaptation to Hypoxia during Lung Development in Chicken
title_sort hypoxia-induced mir-15a promotes mesenchymal ablation and adaptation to hypoxia during lung development in chicken
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041788/
https://www.ncbi.nlm.nih.gov/pubmed/24887070
http://dx.doi.org/10.1371/journal.pone.0098868
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