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Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction
BACKGROUND: Ventilator-induced diaphragmatic dysfunction (VIDD) is associated with weaning difficulties, intensive care unit hospitalization (ICU), infant mortality, and poor long-term clinical outcomes. The expression patterns of long noncoding RNAs (lncRNAs) and mRNAs in the diaphragm in a rat con...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227366/ https://www.ncbi.nlm.nih.gov/pubmed/34172008 http://dx.doi.org/10.1186/s12864-021-07741-9 |
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author | Liu, Ruining Li, Gang Ma, Haoli Zhou, Xianlong Wang, Pengcheng Zhao, Yan |
author_facet | Liu, Ruining Li, Gang Ma, Haoli Zhou, Xianlong Wang, Pengcheng Zhao, Yan |
author_sort | Liu, Ruining |
collection | PubMed |
description | BACKGROUND: Ventilator-induced diaphragmatic dysfunction (VIDD) is associated with weaning difficulties, intensive care unit hospitalization (ICU), infant mortality, and poor long-term clinical outcomes. The expression patterns of long noncoding RNAs (lncRNAs) and mRNAs in the diaphragm in a rat controlled mechanical ventilation (CMV) model, however, remain to be investigated. RESULTS: The diaphragms of five male Wistar rats in a CMV group and five control Wistar rats were used to explore lncRNA and mRNA expression profiles by RNA-sequencing (RNA-seq). Muscle force measurements and immunofluorescence (IF) staining were used to verify the successful establishment of the CMV model. A total of 906 differentially expressed (DE) lncRNAs and 2,139 DE mRNAs were found in the CMV group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the biological functions or pathways of these DE mRNAs. Our results revealed that these DE mRNAs were related mainly related to complement and coagulation cascades, the PPAR signaling pathway, cholesterol metabolism, cytokine-cytokine receptor interaction, and the AMPK signaling pathway. Some DE lncRNAs and DE mRNAs determined by RNA-seq were validated by quantitative real-time polymerase chain reaction (qRT-PCR), which exhibited trends similar to those observed by RNA-sEq. Co-expression network analysis indicated that three selected muscle atrophy-related mRNAs (Myog, Trim63, and Fbxo32) were coexpressed with relatively newly discovered DE lncRNAs. CONCLUSIONS: This study provides a novel perspective on the molecular mechanism of DE lncRNAs and mRNAs in a CMV model, and indicates that the inflammatory signaling pathway and lipid metabolism may play important roles in the pathophysiological mechanism and progression of VIDD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-021-07741-9. |
format | Online Article Text |
id | pubmed-8227366 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-82273662021-06-25 Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction Liu, Ruining Li, Gang Ma, Haoli Zhou, Xianlong Wang, Pengcheng Zhao, Yan BMC Genomics Research Article BACKGROUND: Ventilator-induced diaphragmatic dysfunction (VIDD) is associated with weaning difficulties, intensive care unit hospitalization (ICU), infant mortality, and poor long-term clinical outcomes. The expression patterns of long noncoding RNAs (lncRNAs) and mRNAs in the diaphragm in a rat controlled mechanical ventilation (CMV) model, however, remain to be investigated. RESULTS: The diaphragms of five male Wistar rats in a CMV group and five control Wistar rats were used to explore lncRNA and mRNA expression profiles by RNA-sequencing (RNA-seq). Muscle force measurements and immunofluorescence (IF) staining were used to verify the successful establishment of the CMV model. A total of 906 differentially expressed (DE) lncRNAs and 2,139 DE mRNAs were found in the CMV group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the biological functions or pathways of these DE mRNAs. Our results revealed that these DE mRNAs were related mainly related to complement and coagulation cascades, the PPAR signaling pathway, cholesterol metabolism, cytokine-cytokine receptor interaction, and the AMPK signaling pathway. Some DE lncRNAs and DE mRNAs determined by RNA-seq were validated by quantitative real-time polymerase chain reaction (qRT-PCR), which exhibited trends similar to those observed by RNA-sEq. Co-expression network analysis indicated that three selected muscle atrophy-related mRNAs (Myog, Trim63, and Fbxo32) were coexpressed with relatively newly discovered DE lncRNAs. CONCLUSIONS: This study provides a novel perspective on the molecular mechanism of DE lncRNAs and mRNAs in a CMV model, and indicates that the inflammatory signaling pathway and lipid metabolism may play important roles in the pathophysiological mechanism and progression of VIDD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-021-07741-9. BioMed Central 2021-06-25 /pmc/articles/PMC8227366/ /pubmed/34172008 http://dx.doi.org/10.1186/s12864-021-07741-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Liu, Ruining Li, Gang Ma, Haoli Zhou, Xianlong Wang, Pengcheng Zhao, Yan Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction |
title | Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction |
title_full | Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction |
title_fullStr | Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction |
title_full_unstemmed | Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction |
title_short | Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction |
title_sort | transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227366/ https://www.ncbi.nlm.nih.gov/pubmed/34172008 http://dx.doi.org/10.1186/s12864-021-07741-9 |
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