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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:...

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Autores principales: Gong, Leilei, Lv, Yehua, Li, Shenglong, Feng, Tao, Zhou, Yi, Sun, Yuyu, Mi, Daguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2020
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.
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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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