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Crit Care. 2018 Mar 15;22(1):68. doi: 10.1186/s13054-018-2003-3.

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

Author information

1
Research and Education Institute, Hospital Sirio-Libanes, Rua Professor Daher Cutait 69, São Paulo, SP, 01539-001, Brazil.
2
Sao Paulo State Cancer Institute, University of São Paulo, São Paulo, Brazil.
3
Hospital do Servidor Publico Estadual de São Paulo, São Paulo, Brazil.
4
Morphology Department, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
5
Laboratory of Immunology, Heart Institute, University of São Paulo, School of Medicine, São Paulo, Brazil.
6
Universidade Estadual da Paraíba, Centro de Ciências e Tecnologia, Campina Grande, Brazil.
7
Ludwig Institute for Cancer Research, São Paulo, Brazil.
8
International Research Center, A.C.Camargo Cancer Center, São Paulo, Brazil.
9
Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil.
10
Federal University of São Paulo, São Paulo, Brazil.
11
Research and Education Institute, Hospital Sirio-Libanes, Rua Professor Daher Cutait 69, São Paulo, SP, 01539-001, Brazil. lucianoazevedo@uol.com.br.
12
Emergency Medicine, University of São Paulo, São Paulo, Brazil. lucianoazevedo@uol.com.br.

Abstract

BACKGROUND:

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-fold; PRDX3, 2.6-fold; SOD2, 2.2-fold) and redox-responsive genes (FOXM1, 21-fold; SELS, 16-fold; GLRX2, 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.

KEYWORDS:

Exosomes; Extracellular vesicles; Inflammatory response; Messenger RNA; MicroRNAs; Oxidative stress; Sepsis

PMID:
29540208
PMCID:
PMC5852953
DOI:
10.1186/s13054-018-2003-3
[Indexed for MEDLINE]
Free PMC Article

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