期刊
FRONTIERS IN MOLECULAR BIOSCIENCES
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2022.814240
关键词
miRNA-microRNA; miR-483-3p; let-7d-3p; sepsis-diagnostics; extracellular vehicles (EVs)
资金
- Natural Science Foundation of Zhejiang Province [LYY18H310008, LGF18H150007]
- Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents [2016-6]
- National Natural Science Foundation of China [81671956, 81772122, 82070074]
This study reveals the potential role of plasma EV-miRNAs in the pathogenesis of sepsis and demonstrates the diagnostic value of combining miR-483-3p and let-7d-3p as biomarkers for early sepsis diagnosis.
Background: microRNAs (miRNAs) from circulating extracellular vesicles (EVs) have been reported as disease biomarkers. This study aimed to identify the diagnostic value of plasma EV-miRNAs in sepsis.Methods: EVs were separated from the plasma of sepsis patients at admission and healthy controls. The expression of EV-miRNAs was evaluated by microarray and qRT-PCR.Results: A preliminary miRNA microarray of plasma EVs from a discovery cohort of 3 sepsis patients at admission and three healthy controls identified 11 miRNAs with over 2-fold upregulation in sepsis group. Based on this finding, EV samples from a validation cohort of 37 sepsis patients at admission and 25 healthy controls were evaluated for the expression of the 6 miRNAs relating injury and inflammation via qRT-PCR. Elevated expression of miR-483-3p and let-7d-3p was validated in sepsis patients and corroborated in a mouse model of sepsis. miR-483-3p and let-7d-3p levels positively correlated with the disease severity. Additionally, a combination of miR-483-3p and let-7d-3p had diagnostic value for sepsis. Furthermore, bioinformatic analysis and experimental validation showed that miR-483-3p and let-7d-3p target pathways regulating immune response and endothelial function.Conclusion: The present study reveals the potential role of plasma EV-miRNAs in the pathogenesis of sepsis and the utility of combining miR-483-3p and let-7d-3p as biomarkers for early sepsis diagnosis.
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