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Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis
Traumatic brain injury (TBI) is the leading cause of disability and mortality globally. Melatonin (Mel) is a neuroendocrine hormone synthesized from the pineal gland that protects against TBI. Yet, the precise mechanism of action is not fully understood. In this study, we examined the protective eff...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500234/ https://www.ncbi.nlm.nih.gov/pubmed/36157079 http://dx.doi.org/10.3389/fnmol.2022.974060 |
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author | Fu, Jiayuanyuan Zhou, Qiang Wu, Biying Huang, Xuekang Tang, Zhaohua Tan, Weilin Zhu, Ziyu Du, Mengran Wu, Chenrui Ma, Jun Balawi, Ehab Liao, Z. B. |
author_facet | Fu, Jiayuanyuan Zhou, Qiang Wu, Biying Huang, Xuekang Tang, Zhaohua Tan, Weilin Zhu, Ziyu Du, Mengran Wu, Chenrui Ma, Jun Balawi, Ehab Liao, Z. B. |
author_sort | Fu, Jiayuanyuan |
collection | PubMed |
description | Traumatic brain injury (TBI) is the leading cause of disability and mortality globally. Melatonin (Mel) is a neuroendocrine hormone synthesized from the pineal gland that protects against TBI. Yet, the precise mechanism of action is not fully understood. In this study, we examined the protective effect and regulatory pathways of melatonin in the TBI mice model using transcriptomics and bioinformatics analysis. The expression profiles of mRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) were constructed using the whole transcriptomes sequencing technique. In total, 93 differentially expressed (DE) mRNAs (DEmRNAs), 48 lncRNAs (DElncRNAs), 59 miRNAs (DEmiRNAs), and 59 circRNAs (DEcircRNAs) were identified by the TBI mice with Mel treatment compared to the group without drug intervention. The randomly selected coding RNAs and non-coding RNAs (ncRNAs) were identified by quantitative real-time polymerase chain reaction (qRT-PCR). To further detect the biological functions and potential pathways of those differentially expressed RNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were executed. In our research, the regulatory network was constructed to show the relationship of lncRNA-RBPs. The lncRNA-mRNA co-expression network was established based on the Pearson coefficient to indicate the expression correlations. Moreover, the DEcircRNA–DEmiRNA–DEmRNA and DElncRNA–DEmiRNA–DEmRNA regulatory networks were constructed to demonstrate the regulatory relationship between ncRNAs and mRNA. Finally, to further verify our predicted results, cytoHubba was used to find the hub gene in the synaptic vesicle cycle pathway, and the expression level of SNAP-25 and VAMP-2 after melatonin treatment were detected by Western blotting and immunofluorescence. To sum up, these data offer a new insight regarding the molecular effect of melatonin treatment after TBI and suggest that the high-throughput sequencing and analysis of transcriptomes are useful for studying the drug mechanisms in treatment after TBI. |
format | Online Article Text |
id | pubmed-9500234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95002342022-09-24 Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis Fu, Jiayuanyuan Zhou, Qiang Wu, Biying Huang, Xuekang Tang, Zhaohua Tan, Weilin Zhu, Ziyu Du, Mengran Wu, Chenrui Ma, Jun Balawi, Ehab Liao, Z. B. Front Mol Neurosci Neuroscience Traumatic brain injury (TBI) is the leading cause of disability and mortality globally. Melatonin (Mel) is a neuroendocrine hormone synthesized from the pineal gland that protects against TBI. Yet, the precise mechanism of action is not fully understood. In this study, we examined the protective effect and regulatory pathways of melatonin in the TBI mice model using transcriptomics and bioinformatics analysis. The expression profiles of mRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) were constructed using the whole transcriptomes sequencing technique. In total, 93 differentially expressed (DE) mRNAs (DEmRNAs), 48 lncRNAs (DElncRNAs), 59 miRNAs (DEmiRNAs), and 59 circRNAs (DEcircRNAs) were identified by the TBI mice with Mel treatment compared to the group without drug intervention. The randomly selected coding RNAs and non-coding RNAs (ncRNAs) were identified by quantitative real-time polymerase chain reaction (qRT-PCR). To further detect the biological functions and potential pathways of those differentially expressed RNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were executed. In our research, the regulatory network was constructed to show the relationship of lncRNA-RBPs. The lncRNA-mRNA co-expression network was established based on the Pearson coefficient to indicate the expression correlations. Moreover, the DEcircRNA–DEmiRNA–DEmRNA and DElncRNA–DEmiRNA–DEmRNA regulatory networks were constructed to demonstrate the regulatory relationship between ncRNAs and mRNA. Finally, to further verify our predicted results, cytoHubba was used to find the hub gene in the synaptic vesicle cycle pathway, and the expression level of SNAP-25 and VAMP-2 after melatonin treatment were detected by Western blotting and immunofluorescence. To sum up, these data offer a new insight regarding the molecular effect of melatonin treatment after TBI and suggest that the high-throughput sequencing and analysis of transcriptomes are useful for studying the drug mechanisms in treatment after TBI. Frontiers Media S.A. 2022-09-09 /pmc/articles/PMC9500234/ /pubmed/36157079 http://dx.doi.org/10.3389/fnmol.2022.974060 Text en Copyright © 2022 Fu, Zhou, Wu, Huang, Tang, Tan, Zhu, Du, Wu, Ma, Balawi and Liao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Fu, Jiayuanyuan Zhou, Qiang Wu, Biying Huang, Xuekang Tang, Zhaohua Tan, Weilin Zhu, Ziyu Du, Mengran Wu, Chenrui Ma, Jun Balawi, Ehab Liao, Z. B. Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis |
title | Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis |
title_full | Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis |
title_fullStr | Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis |
title_full_unstemmed | Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis |
title_short | Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis |
title_sort | protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: transcriptomics and bioinformatics analysis |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500234/ https://www.ncbi.nlm.nih.gov/pubmed/36157079 http://dx.doi.org/10.3389/fnmol.2022.974060 |
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