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Changes in transcriptome profiling during the acute/subacute phases of contusional spinal cord injury in rats
BACKGROUND: Spinal cord injuries (SCIs), along with subsequent secondary injuries, often result in irreversible damage to both sensory and motor functions. However, a thorough view of the underlying pathological mechanisms of SCIs, especially in a temporal-spatial manner, is still lacking. METHODS:...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812200/ https://www.ncbi.nlm.nih.gov/pubmed/33490194 http://dx.doi.org/10.21037/atm-20-6519 |
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author | Gong, Leilei Lv, Yehua Li, Shenglong Feng, Tao Zhou, Yi Sun, Yuyu Mi, Daguo |
author_facet | Gong, Leilei Lv, Yehua Li, Shenglong Feng, Tao Zhou, Yi Sun, Yuyu Mi, Daguo |
author_sort | Gong, Leilei |
collection | PubMed |
description | BACKGROUND: Spinal cord injuries (SCIs), along with subsequent secondary injuries, often result in irreversible damage to both sensory and motor functions. However, a thorough view of the underlying pathological mechanisms of SCIs, especially in a temporal-spatial manner, is still lacking. METHODS: To obtain a comprehensive, real-time view of multiple subsets of the cellular mechanisms involved in SCIs, we applied RNA-sequencing technology to characterize the temporal changes in gene expression around the lesion site of contusion SCI in rats. First, we identified the differentially expressed genes (DEGs) in contrast to sham controls at 1, 4, and 7 days post SCI. Through bioinformatics analysis, including Pathway analysis, Gene-act-net, and Pathway-act-net, we screened and verified potential key pathways and genes associated with either the acute or subacute stages of SCI pathology. RESULTS: The top three overrepresented pathways were associated with cytokine-cytokine receptor interaction, TNF signaling pathway, and cell cycle at day 1; lysosome, cytokine-cytokine receptor interaction, phagosome at day 4; and phagosome, lysosome, cytokine-cytokine receptor interaction at day 7 post injury. Further, we identified uniquely enriched genes at each time point, such as Ccr1 and Nos2 at day 1; as well as Mgst2, and Pla2g3 at 4 and 7 days post-injury. CONCLUSIONS: Our pathway analysis suggested a transition from inflammatory responses to multiple forms of cell death processes from the acute to subacute stages of SCI. Further, our results revealed a continuous transformation from a more inflammatory to an apoptotic/self-repairing transcriptome following the time-course of SCIs. Our research provides novel insights into the molecular mechanisms of SCI pathophysiology and identifies potential targets for therapeutic intervention after SCI. |
format | Online Article Text |
id | pubmed-7812200 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-78122002021-01-22 Changes in transcriptome profiling during the acute/subacute phases of contusional spinal cord injury in rats Gong, Leilei Lv, Yehua Li, Shenglong Feng, Tao Zhou, Yi Sun, Yuyu Mi, Daguo Ann Transl Med Original Article BACKGROUND: Spinal cord injuries (SCIs), along with subsequent secondary injuries, often result in irreversible damage to both sensory and motor functions. However, a thorough view of the underlying pathological mechanisms of SCIs, especially in a temporal-spatial manner, is still lacking. METHODS: To obtain a comprehensive, real-time view of multiple subsets of the cellular mechanisms involved in SCIs, we applied RNA-sequencing technology to characterize the temporal changes in gene expression around the lesion site of contusion SCI in rats. First, we identified the differentially expressed genes (DEGs) in contrast to sham controls at 1, 4, and 7 days post SCI. Through bioinformatics analysis, including Pathway analysis, Gene-act-net, and Pathway-act-net, we screened and verified potential key pathways and genes associated with either the acute or subacute stages of SCI pathology. RESULTS: The top three overrepresented pathways were associated with cytokine-cytokine receptor interaction, TNF signaling pathway, and cell cycle at day 1; lysosome, cytokine-cytokine receptor interaction, phagosome at day 4; and phagosome, lysosome, cytokine-cytokine receptor interaction at day 7 post injury. Further, we identified uniquely enriched genes at each time point, such as Ccr1 and Nos2 at day 1; as well as Mgst2, and Pla2g3 at 4 and 7 days post-injury. CONCLUSIONS: Our pathway analysis suggested a transition from inflammatory responses to multiple forms of cell death processes from the acute to subacute stages of SCI. Further, our results revealed a continuous transformation from a more inflammatory to an apoptotic/self-repairing transcriptome following the time-course of SCIs. Our research provides novel insights into the molecular mechanisms of SCI pathophysiology and identifies potential targets for therapeutic intervention after SCI. AME Publishing Company 2020-12 /pmc/articles/PMC7812200/ /pubmed/33490194 http://dx.doi.org/10.21037/atm-20-6519 Text en 2020 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Gong, Leilei Lv, Yehua Li, Shenglong Feng, Tao Zhou, Yi Sun, Yuyu Mi, Daguo Changes in transcriptome profiling during the acute/subacute phases of contusional spinal cord injury in rats |
title | Changes in transcriptome profiling during the acute/subacute phases of contusional spinal cord injury in rats |
title_full | Changes in transcriptome profiling during the acute/subacute phases of contusional spinal cord injury in rats |
title_fullStr | Changes in transcriptome profiling during the acute/subacute phases of contusional spinal cord injury in rats |
title_full_unstemmed | Changes in transcriptome profiling during the acute/subacute phases of contusional spinal cord injury in rats |
title_short | Changes in transcriptome profiling during the acute/subacute phases of contusional spinal cord injury in rats |
title_sort | changes in transcriptome profiling during the acute/subacute phases of contusional spinal cord injury in rats |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812200/ https://www.ncbi.nlm.nih.gov/pubmed/33490194 http://dx.doi.org/10.21037/atm-20-6519 |
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