Cellular and extracellular miRNAs are blood-compartment-specific diagnostic targets in sepsis.

Abstract

Septic shock is a common medical condition with a mortality approaching 50% where early diagnosis and treatment are of particular importance for patient survival. Novel biomarkers that serve as prompt indicators of sepsis are urgently needed. High-throughput technologies assessing circulating microRNAs represent an important tool for biomarker identification, but the blood-compartment specificity of these miRNAs has not yet been investigated. We characterized miRNA profiles from serum exosomes, total serum and blood cells (leukocytes, erythrocytes, platelets) of sepsis patients by next-generation sequencing and RT-qPCR (n = 3 × 22) and established differences in miRNA expression between blood compartments. In silico analysis was used to identify compartment-specific signalling functions of differentially regulated miRNAs in sepsis-relevant pathways. In septic shock, a total of 77 and 103 miRNAs were down- and up-regulated, respectively. A majority of these regulated miRNAs (14 in serum, 32 in exosomes and 73 in blood cells) had not been previously associated with sepsis. We found a distinctly compartment-specific regulation of miRNAs between sepsis patients and healthy volunteers. Blood cellular miR-199b-5p was identified as a potential early indicator for sepsis and septic shock. miR-125b-5p and miR-26b-5p were uniquely regulated in exosomes and serum, respectively, while one miRNA (miR-27b-3p) was present in all three compartments. The expression of sepsis-associated miRNAs is compartment-specific. Exosome-derived miRNAs contribute significant information regarding sepsis diagnosis and survival prediction and could serve as newly identified targets for the development of novel sepsis biomarkers.

• Authors: Marlene Reithmair, Dominik Buschmann, Melanie Märte, Benedikt Kirchner, Daniel Hagl, Ines Kaufmann, Martina Pfob, Alexander Chouker, Ortrud K Steinlein, Michael W Pfaffl, Gustav Schelling
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 21 Issue 10 Pg. 2403-2411 (10 2017) ISSN: 1582-4934 [Electronic] England
• PMID: 28382754 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Biomarkers
• MicroRNAs

Topics

• Biomarkers (blood)
• Blood Platelets (metabolism)
• Erythrocytes (metabolism)
• Exosomes (genetics, ultrastructure)
• Gene Expression Profiling (methods)
• Humans
• Leukocytes (metabolism)
• MicroRNAs (blood, genetics)
• Microscopy, Electron, Transmission
• Prognosis
• Sepsis (blood, diagnosis, genetics)