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Transcriptomic-Metabolomic Profiling in Mouse Lung Tissues Reveals Sex- and Strain-Based Differences
Omics analyses are commonly used for identifying pathways and genes responsible for physiologic and pathologic processes. Though sex is considered a biological variable in rigorous assessments of pulmonary responses to oxidant exposures, the contribution of the murine strain is largely ignored. This...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612261/ https://www.ncbi.nlm.nih.gov/pubmed/36295835 http://dx.doi.org/10.3390/metabo12100932 |
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author | Fernandes, Jolyn Dunigan-Russell, Katelyn Zhong, Hua Lin, Vivian Silverberg, Mary Moore, Stephanie B. Tran, ViLinh Jones, Dean P. Vitiello, Peter F. Rogers, Lynette K. Tipple, Trent E. |
author_facet | Fernandes, Jolyn Dunigan-Russell, Katelyn Zhong, Hua Lin, Vivian Silverberg, Mary Moore, Stephanie B. Tran, ViLinh Jones, Dean P. Vitiello, Peter F. Rogers, Lynette K. Tipple, Trent E. |
author_sort | Fernandes, Jolyn |
collection | PubMed |
description | Omics analyses are commonly used for identifying pathways and genes responsible for physiologic and pathologic processes. Though sex is considered a biological variable in rigorous assessments of pulmonary responses to oxidant exposures, the contribution of the murine strain is largely ignored. This study utilized an unbiased integrated assessment of high-resolution metabolomic profiling and RNA-sequencing to explore sex- and strain-dependent pathways in adult mouse lungs. The results indicated that strain exhibited a greater influence than sex on pathways associated with inflammatory and oxidant/antioxidant responses and that interaction metabolites more closely resembled those identified as differentially expressed by strain. Metabolite analyses revealed that the components of the glutathione antioxidant pathway were different between strains, specifically in the formation of mixed disulfides. Additionally, selenium metabolites such as selenohomocystiene and selenocystathionine were similarly differentially expressed. Transcriptomic analysis revealed similar findings, as evidenced by differences in glutathione peroxidase, peroxiredoxin, and the inflammatory transcription factors RelA and Jun. In summary, an multi-omics integrated approach identified that murine strain disproportionately impacts baseline expression of antioxidant systems in lung tissues. We speculate that strain-dependent differences contribute to discrepant pulmonary responses in preclincal mouse models, with deleterious effects on clinical translation. |
format | Online Article Text |
id | pubmed-9612261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96122612022-10-28 Transcriptomic-Metabolomic Profiling in Mouse Lung Tissues Reveals Sex- and Strain-Based Differences Fernandes, Jolyn Dunigan-Russell, Katelyn Zhong, Hua Lin, Vivian Silverberg, Mary Moore, Stephanie B. Tran, ViLinh Jones, Dean P. Vitiello, Peter F. Rogers, Lynette K. Tipple, Trent E. Metabolites Article Omics analyses are commonly used for identifying pathways and genes responsible for physiologic and pathologic processes. Though sex is considered a biological variable in rigorous assessments of pulmonary responses to oxidant exposures, the contribution of the murine strain is largely ignored. This study utilized an unbiased integrated assessment of high-resolution metabolomic profiling and RNA-sequencing to explore sex- and strain-dependent pathways in adult mouse lungs. The results indicated that strain exhibited a greater influence than sex on pathways associated with inflammatory and oxidant/antioxidant responses and that interaction metabolites more closely resembled those identified as differentially expressed by strain. Metabolite analyses revealed that the components of the glutathione antioxidant pathway were different between strains, specifically in the formation of mixed disulfides. Additionally, selenium metabolites such as selenohomocystiene and selenocystathionine were similarly differentially expressed. Transcriptomic analysis revealed similar findings, as evidenced by differences in glutathione peroxidase, peroxiredoxin, and the inflammatory transcription factors RelA and Jun. In summary, an multi-omics integrated approach identified that murine strain disproportionately impacts baseline expression of antioxidant systems in lung tissues. We speculate that strain-dependent differences contribute to discrepant pulmonary responses in preclincal mouse models, with deleterious effects on clinical translation. MDPI 2022-09-30 /pmc/articles/PMC9612261/ /pubmed/36295835 http://dx.doi.org/10.3390/metabo12100932 Text en © 2022 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 Fernandes, Jolyn Dunigan-Russell, Katelyn Zhong, Hua Lin, Vivian Silverberg, Mary Moore, Stephanie B. Tran, ViLinh Jones, Dean P. Vitiello, Peter F. Rogers, Lynette K. Tipple, Trent E. Transcriptomic-Metabolomic Profiling in Mouse Lung Tissues Reveals Sex- and Strain-Based Differences |
title | Transcriptomic-Metabolomic Profiling in Mouse Lung Tissues Reveals Sex- and Strain-Based Differences |
title_full | Transcriptomic-Metabolomic Profiling in Mouse Lung Tissues Reveals Sex- and Strain-Based Differences |
title_fullStr | Transcriptomic-Metabolomic Profiling in Mouse Lung Tissues Reveals Sex- and Strain-Based Differences |
title_full_unstemmed | Transcriptomic-Metabolomic Profiling in Mouse Lung Tissues Reveals Sex- and Strain-Based Differences |
title_short | Transcriptomic-Metabolomic Profiling in Mouse Lung Tissues Reveals Sex- and Strain-Based Differences |
title_sort | transcriptomic-metabolomic profiling in mouse lung tissues reveals sex- and strain-based differences |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612261/ https://www.ncbi.nlm.nih.gov/pubmed/36295835 http://dx.doi.org/10.3390/metabo12100932 |
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