Exosomes from patients with septic shock convey miRNAs related to inflammation and cell cycle regulation: new signaling pathways in sepsis?
Exosomes from patients with septic shock convey miRNAs related to inflammation and cell cycle regulation: new signaling pathways in sepsis?
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DOI：
10.1186/s13054-018-2003-3
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发表时间：
2018-03-15
期刊：
影响因子：
--
通讯作者：
Azevedo LCP
中科院分区：
文献类型：
--
作者：
Real JM;Ferreira LRP;Esteves GH;Koyama FC;Dias MVS;Bezerra-Neto JE;Cunha-Neto E;Machado FR;Salomão R;Azevedo LCP
从脓毒症患者血浆中分离的外泌体可能通过与炎症和氧化应激相关的机制诱导血管凋亡和心肌功能障碍。尽管先前的研究表明这些囊泡含有与细胞通讯相关的遗传物质，但脓毒症期间它们的分子货物相对未知。在这项研究中，我们评估了感染性休克患者外泌体中与炎症反应和氧化还原代谢相关的microRNA（miRNAs）和信使RNA（mRNAs）的存在。在ICU入院时和治疗7天后，从24名感染性休克患者中采集血液样本。12名健康志愿者作为对照组。通过超离心分离外泌体，并通过qRT-PCR阵列评估其miRNA和mRNA含量。与健康志愿者相比，来自脓毒症患者的exosomal在65个exosomal miRNAs中有显著变化。28种miRNA在入组时和7天后差异表达，具有相似的动力学（18种miRNA上调，10种下调）。在招募时，35个差异表达的miRNA根据生存率将脓毒症患者聚类。与对照组相比，脓毒症患者miRNAs富集的途径主要与炎症反应相关。根据医院生存率对来自脓毒症患者的miRNA进行比较，证明了主要与细胞周期调控相关的途径。在入组时，脓毒症与氧化还原代谢相关mRNA（髓过氧化物酶，64倍; PRDX 3，2.6倍; SOD 2，2.2倍）和氧化还原反应基因（FOXM 1，21倍; SELS，16倍; GLRX 2，3.4倍）的表达显著增加相关。髓过氧化物酶mRNA的表达在7天后仍然升高（65倍）。来自感染性休克患者的外泌体表达与致病途径相关的miRNA和mRNA，包括炎症反应、氧化应激和细胞周期调节。外泌体可能代表脓毒症期间细胞间通讯的新机制。本文的在线版本（10.1186/s13054-018-2003-3）包含补充材料，可供授权用户使用。
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. 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. 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). 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. The online version of this article (10.1186/s13054-018-2003-3) contains supplementary material, which is available to authorized users.
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影响因子：
4.1
作者：
Ferry, G;Ubeaud, C;Boutin, JA
通讯作者：
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DOI：
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