Time-course full profiling of circulating miRNAs in neurologically deceased organ donors: a proof of concept study to understand the onset of the cytokine storm
Neurologically deceased organ donors (NDDs) generally display an immune response involving an intense production of pro-inflammatory cytokines referred to as the cytokine storm. The sudden surge of inflammatory mediators in circulation promotes tissue and organ damages and ultimately leads to poor t...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-11-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2022.2076048 |
| _version_ | 1797678811801714688 |
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| author | Andrée-Anne Clément Daphnée Lamarche Marie-Hélène Masse Cécilia Légaré Lee-Hwa Tai Laurence Fleury Deland Marie-Claude Battista Luigi Bouchard Frédérick D’Aragon |
| author_facet | Andrée-Anne Clément Daphnée Lamarche Marie-Hélène Masse Cécilia Légaré Lee-Hwa Tai Laurence Fleury Deland Marie-Claude Battista Luigi Bouchard Frédérick D’Aragon |
| author_sort | Andrée-Anne Clément |
| collection | DOAJ |
| description | Neurologically deceased organ donors (NDDs) generally display an immune response involving an intense production of pro-inflammatory cytokines referred to as the cytokine storm. The sudden surge of inflammatory mediators in circulation promotes tissue and organ damages and ultimately leads to poor transplant outcome. As microRNAs (miRNAs) are frequently proposed as key regulators of inflammation and are relatively stable in circulation, changes in their profiles could play a role in the onset of the cytokine storm in NDDs. In this proof-of-concept study, we sought to investigate differentially abundant circulating miRNAs in a temporal manner between neurological death and organ recovery and to assess the association between specific miRNAs and levels of inflammatory cytokines in blood. Plasma samples from five NDDs were obtained at multiple time points between organ donation consent and organ recovery. Using a time-course analysis and miRNA sequencing, we identified 32 plasma miRNAs fluctuating between consent and organ recovery (false discovery rate; q-value < 0.1). Eleven miRNAs relatively abundant (>100 reads) and detected in all samples were selected for further biological pathway analysis (miR-486-3p, miR-103a-3p, miR-106b-3p, miR-182-5p, miR-101-3p, miR-10a-5p, miR-125a-5p, miR-146b-5p, miR-26a-5p, miR-423-5p, miR-92b-3p). These miRNAs targeted genes such as c-JUN (TNF signalling pathway) and eEF2 (AMPK pathway), suggesting a potential role in regulation of inflammation. Our results contribute to a better understanding of the miRNAs dynamic after neurological death in organ donors and could potentially be used to predict the related early cytokine storm.Trial registration: ClinicalTrials.gov ID NCT03786991. Registered December 2018 |
| first_indexed | 2024-03-11T23:05:21Z |
| format | Article |
| id | doaj.art-48b612bb75bf41168c5992ee951c0137 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:05:21Z |
| publishDate | 2022-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-48b612bb75bf41168c5992ee951c01372023-09-21T13:23:12ZengTaylor & Francis GroupEpigenetics1559-22941559-23082022-11-0117111546156110.1080/15592294.2022.20760482076048Time-course full profiling of circulating miRNAs in neurologically deceased organ donors: a proof of concept study to understand the onset of the cytokine stormAndrée-Anne Clément0Daphnée Lamarche1Marie-Hélène Masse2Cécilia Légaré3Lee-Hwa Tai4Laurence Fleury Deland5Marie-Claude Battista6Luigi Bouchard7Frédérick D’Aragon8Université de SherbrookeFMHS,Université de SherbrookeCentre de Recherche du Centre Hospitalier Universitaire de SherbrookeUniversité de SherbrookeCentre de Recherche du Centre Hospitalier Universitaire de SherbrookeFMHS,Université de SherbrookeFMHS,Université de SherbrookeUniversité de SherbrookeFMHS,Université de SherbrookeNeurologically deceased organ donors (NDDs) generally display an immune response involving an intense production of pro-inflammatory cytokines referred to as the cytokine storm. The sudden surge of inflammatory mediators in circulation promotes tissue and organ damages and ultimately leads to poor transplant outcome. As microRNAs (miRNAs) are frequently proposed as key regulators of inflammation and are relatively stable in circulation, changes in their profiles could play a role in the onset of the cytokine storm in NDDs. In this proof-of-concept study, we sought to investigate differentially abundant circulating miRNAs in a temporal manner between neurological death and organ recovery and to assess the association between specific miRNAs and levels of inflammatory cytokines in blood. Plasma samples from five NDDs were obtained at multiple time points between organ donation consent and organ recovery. Using a time-course analysis and miRNA sequencing, we identified 32 plasma miRNAs fluctuating between consent and organ recovery (false discovery rate; q-value < 0.1). Eleven miRNAs relatively abundant (>100 reads) and detected in all samples were selected for further biological pathway analysis (miR-486-3p, miR-103a-3p, miR-106b-3p, miR-182-5p, miR-101-3p, miR-10a-5p, miR-125a-5p, miR-146b-5p, miR-26a-5p, miR-423-5p, miR-92b-3p). These miRNAs targeted genes such as c-JUN (TNF signalling pathway) and eEF2 (AMPK pathway), suggesting a potential role in regulation of inflammation. Our results contribute to a better understanding of the miRNAs dynamic after neurological death in organ donors and could potentially be used to predict the related early cytokine storm.Trial registration: ClinicalTrials.gov ID NCT03786991. Registered December 2018http://dx.doi.org/10.1080/15592294.2022.2076048organ donationtransplantationcirculating mirnasmicrornasnext-generation sequencingmicrotranscriptome |
| spellingShingle | Andrée-Anne Clément Daphnée Lamarche Marie-Hélène Masse Cécilia Légaré Lee-Hwa Tai Laurence Fleury Deland Marie-Claude Battista Luigi Bouchard Frédérick D’Aragon Time-course full profiling of circulating miRNAs in neurologically deceased organ donors: a proof of concept study to understand the onset of the cytokine storm Epigenetics organ donation transplantation circulating mirnas micrornas next-generation sequencing microtranscriptome |
| title | Time-course full profiling of circulating miRNAs in neurologically deceased organ donors: a proof of concept study to understand the onset of the cytokine storm |
| title_full | Time-course full profiling of circulating miRNAs in neurologically deceased organ donors: a proof of concept study to understand the onset of the cytokine storm |
| title_fullStr | Time-course full profiling of circulating miRNAs in neurologically deceased organ donors: a proof of concept study to understand the onset of the cytokine storm |
| title_full_unstemmed | Time-course full profiling of circulating miRNAs in neurologically deceased organ donors: a proof of concept study to understand the onset of the cytokine storm |
| title_short | Time-course full profiling of circulating miRNAs in neurologically deceased organ donors: a proof of concept study to understand the onset of the cytokine storm |
| title_sort | time course full profiling of circulating mirnas in neurologically deceased organ donors a proof of concept study to understand the onset of the cytokine storm |
| topic | organ donation transplantation circulating mirnas micrornas next-generation sequencing microtranscriptome |
| url | http://dx.doi.org/10.1080/15592294.2022.2076048 |
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