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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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