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Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice

Retinoids are potent transcriptional regulators that act in regulating cell proliferation, differentiation, and other cellular processes. We carried out studies in male mice to establish the importance of local cellular retinoid stores within the lung alveolus for maintaining its health in the face...

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Autores principales: Shmarakov, Igor O., Gusarova, Galina A., Islam, Mohammad N., Marhuenda-Muñoz, María, Bhattacharya, Jahar, Blaner, William S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932169/
https://www.ncbi.nlm.nih.gov/pubmed/36792627
http://dx.doi.org/10.1038/s41467-023-36475-3
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author Shmarakov, Igor O.
Gusarova, Galina A.
Islam, Mohammad N.
Marhuenda-Muñoz, María
Bhattacharya, Jahar
Blaner, William S.
author_facet Shmarakov, Igor O.
Gusarova, Galina A.
Islam, Mohammad N.
Marhuenda-Muñoz, María
Bhattacharya, Jahar
Blaner, William S.
author_sort Shmarakov, Igor O.
collection PubMed
description Retinoids are potent transcriptional regulators that act in regulating cell proliferation, differentiation, and other cellular processes. We carried out studies in male mice to establish the importance of local cellular retinoid stores within the lung alveolus for maintaining its health in the face of an acute inflammatory challenge induced by intranasal instillation of lipopolysaccharide. We also undertook single cell RNA sequencing and bioinformatic analyses to identify roles for different alveolar cell populations involved in mediating these retinoid-dependent responses. Here we show that local retinoid stores and uncompromised metabolism and signaling within the lung are required to lessen the severity of an acute inflammatory challenge. Unexpectedly, our data also establish that alveolar cells other than lipofibroblasts, specifically microvascular endothelial and alveolar epithelial cells, are able to take up lipoprotein-transported retinoid and to accumulate cellular retinoid stores that are directly used to respond to an acute inflammatory challenge.
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spelling pubmed-99321692023-02-17 Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice Shmarakov, Igor O. Gusarova, Galina A. Islam, Mohammad N. Marhuenda-Muñoz, María Bhattacharya, Jahar Blaner, William S. Nat Commun Article Retinoids are potent transcriptional regulators that act in regulating cell proliferation, differentiation, and other cellular processes. We carried out studies in male mice to establish the importance of local cellular retinoid stores within the lung alveolus for maintaining its health in the face of an acute inflammatory challenge induced by intranasal instillation of lipopolysaccharide. We also undertook single cell RNA sequencing and bioinformatic analyses to identify roles for different alveolar cell populations involved in mediating these retinoid-dependent responses. Here we show that local retinoid stores and uncompromised metabolism and signaling within the lung are required to lessen the severity of an acute inflammatory challenge. Unexpectedly, our data also establish that alveolar cells other than lipofibroblasts, specifically microvascular endothelial and alveolar epithelial cells, are able to take up lipoprotein-transported retinoid and to accumulate cellular retinoid stores that are directly used to respond to an acute inflammatory challenge. Nature Publishing Group UK 2023-02-15 /pmc/articles/PMC9932169/ /pubmed/36792627 http://dx.doi.org/10.1038/s41467-023-36475-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Shmarakov, Igor O.
Gusarova, Galina A.
Islam, Mohammad N.
Marhuenda-Muñoz, María
Bhattacharya, Jahar
Blaner, William S.
Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice
title Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice
title_full Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice
title_fullStr Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice
title_full_unstemmed Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice
title_short Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice
title_sort retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932169/
https://www.ncbi.nlm.nih.gov/pubmed/36792627
http://dx.doi.org/10.1038/s41467-023-36475-3
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