Cellular and extracellular miRNAs are blood-compartment-specific diagnostic targets in sepsis
Cellular and extracellular miRNAs are blood-compartment-specific diagnostic targets in sepsis
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DOI：
10.1111/jcmm.13162
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发表时间：
2017-10-01
影响因子：
5.3
通讯作者：
Schelling, Gustav
中科院分区：
文献类型：
--
作者：
Reithmair, Marlene;Buschmann, Dominik;Schelling, Gustav
感染性休克是一种常见的内科疾病，死亡率接近50%，早期诊断和治疗对患者的生存尤为重要。迫切需要新的生物标志物作为脓毒症的及时指标。高通量技术评估循环microRNAs是鉴定生物标记物的重要工具，但这些miRNAs的血隔室特异性尚未被研究。我们用下一代测序和RT-qPCR(n=3x22)分析了脓毒症患者血清外体、总血清和血细胞(白细胞、红细胞、血小板)的miRNA谱，并建立了不同血室间miRNA表达的差异。在计算机分析中，用来确定脓毒症相关通路中差异调控的miRNAs的区室特异性信号功能。在感染性休克中，共有77个和103个miRNAs表达下调和上调。这些受调控的miRNAs中的大多数(14个在血清中，32个在外体中，73个在血细胞中)以前从未与脓毒症相关。我们发现，在脓毒症患者和健康志愿者之间，miRNAs具有明显的区室特异性调节。血细胞miR-199B-5p被认为是脓毒症和感染性休克的潜在早期指标。MiR-125b-5p和miR-26b-5p分别在外切体和血清中唯一调控，而miRNA(miR-27b-3p)存在于三个区段中。脓毒症相关miRNAs的表达具有区室特异性。外切体来源的miRNAs为脓毒症的诊断和生存预测提供了重要的信息，并可作为开发新的败血症生物标志物的新靶点。
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=3x22) 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.