Exosomes from patients with septic shock convey miRNAs related to inflammation and cell cycle regulation: new signaling pathways in sepsis?

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dc.citation.volumev. 22
dc.contributor.authorReal, Juliana Monte
dc.contributor.authorFerreira, Ludmila Rodrigues Pinto
dc.contributor.authorEsteves, Gustavo Henrique
dc.contributor.authorKoyama, Fernanda Christtanini
dc.contributor.authorDias, Marcos Vinicius Salles
dc.contributor.authorBezerra-Neto, Joao Evangelista
dc.contributor.authorCunha-Neto, Edecio
dc.contributor.authorMachado, Flavia Ribeiro [UNIFESP]
dc.contributor.authorSalomão, Reinaldo [UNIFESP]
dc.contributor.authorAzevedo, Luciano Cesar Pontes
dc.coverageLondon
dc.date.accessioned2020-07-20T16:31:14Z
dc.date.available2020-07-20T16:31:14Z
dc.date.issued2018
dc.description.abstractBackground: Exosomes isolated from plasma of patients with sepsis may induce vascular apoptosis and myocardial dysfunction by mechanisms related to inflammation and oxidative stress. Despite previous studies demonstrating that these vesicles contain genetic material related to cellular communication, their molecular cargo during sepsis is relatively unknown. In this study, we evaluated the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) related to inflammatory response and redox metabolism in exosomes of patients with septic shock. Methods: Blood samples were collected from 24 patients with septic shock at ICU admission and after 7 days of treatment. Twelve healthy volunteers were used as control subjects. Exosomes were isolated by ultracentrifugation, and their miRNA and mRNA content was evaluated by qRT-PCR array. Results: As compared with healthy volunteers, exosomes from patients with sepsis had significant changes in 65 exosomal miRNAs. Twenty-eight miRNAs were differentially expressed, both at enrollment and after 7 days, with similar kinetics (18 miRNAs upregulated and 10 downregulated). At enrollment, 35 differentially expressed miRNAs clustered patients with sepsis according to survival. The pathways enriched by the miRNAs of patients with sepsis compared with control subjects were related mostly to inflammatory response. The comparison of miRNAs from patients with sepsis according to hospital survival demonstrated pathways related mostly to cell cycle regulation. At enrollment, sepsis was associated with significant increases in the expression of mRNAs related to redox metabolism (myeloperoxidase, 64-folden
dc.description.abstractPRDX3, 2.6-folden
dc.description.abstractSOD2, 2.2-fold) and redox-responsive genes (FOXM1, 21-folden
dc.description.abstractSELS, 16-folden
dc.description.abstractGLRX2, 3.4-fold). The expression of myeloperoxidase mRNA remained elevated after 7 days (65-fold). Conclusions: Exosomes from patients with septic shock convey miRNAs and mRNAs related to pathogenic pathways, including inflammatory response, oxidative stress, and cell cycle regulation. Exosomes may represent a novel mechanism for intercellular communication during sepsis.en
dc.description.affiliationHosp Sirio Libanes, Res & Educ Inst, Rua Prof Daher Cutait 69, BR-01539001 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Sao Paulo State Canc Inst, Sao Paulo, Brazil
dc.description.affiliationHosp Serv Publ Estadual Sao Paulo, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Minas Gerais, Inst Ciencias Biol, Morphol Dept, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Sao Paulo, Sch Med, Heart Inst, Lab Immunol, Sao Paulo, Brazil
dc.description.affiliationUniv Estadual Paraiba, Ctr Ciencias & Tecnol, Campina Grande, Brazil
dc.description.affiliationLudwig Inst Canc Res, Sao Paulo, Brazil
dc.description.affiliationAC Camargo Canc Ctr, Int Res Ctr, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Emergency Med, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipResearch and Education Institute, Hospital Sirio-Libanes
dc.description.sponsorshipIDFAPESP: 10/52554-1
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1186/s13054-018-2003-3
dc.identifier.citationCritical Care. London, v. 22, 2018.
dc.identifier.doi10.1186/s13054-018-2003-3
dc.identifier.fileWOS000427698000001.pdf
dc.identifier.issn1466-609X
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55813
dc.identifier.wosWOS:000427698000001
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofCritical Care
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectSepsisen
dc.subjectExtracellular vesiclesen
dc.subjectExosomesen
dc.subjectMicroRNAsen
dc.subjectMessenger RNAen
dc.subjectInflammatory responseen
dc.subjectOxidative stressen
dc.titleExosomes from patients with septic shock convey miRNAs related to inflammation and cell cycle regulation: new signaling pathways in sepsis?en
dc.typeinfo:eu-repo/semantics/article
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