Urine-derived extracellular vesicle miRNAs as possible biomarkers for and mediators of necrotizing enterocolitis: A proof of concept study.
Urine-derived extracellular vesicle miRNAs as possible biomarkers for and mediators of necrotizing enterocolitis: A proof of concept study.
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DOI：
10.1016/j.jpedsurg.2021.02.016
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发表时间：
2021-11
影响因子：
2.4
通讯作者：
Besner GE
中科院分区：
文献类型：
--
作者：
Galley JD;Mar P;Wang Y;Han R;Rajab A;Besner GE
坏死性小肠结肠炎（NEC）的早期症状与非NEC败血症的表现相似，尽管治疗方案根据抗生素给药和不喂饲料而有所不同。改进的NEC分化诊断将使临床医生能够更快地将个体患者置于靶向治疗路径上。细胞外囊泡衍生的mirna先前已被证明是疾病生物标志物。为了确定这些mirna在NEC婴儿中是否存在差异表达，我们对尿源性细胞外囊泡mirna进行了转录组学分析。从四组（n≥8）中的一组（医学NEC、外科NEC、非NEC败血症和年龄匹配的健康对照组）的婴儿中无创获取尿液。分离ev衍生的mirna并进行转录组学分析。多个mirna，包括miR-376a， miR-518a-3p和miR-604，在NEC与非NEC败血症和健康对照组的比较中显着改变，并且可能被用作特定的NEC生物标志物。此外，独创性通路分析表明，NEC中差异表达的miRs与炎症性疾病和肠道疾病相关。与NEC相关的信号转导分子包括TP53和RPS15，它们在NEC大鼠模型中也被转录减少。这些数据表明，在NEC与非NEC败血症和年龄匹配对照的分化中，有一组潜在的尿液ev衍生mirna可能被验证为NEC生物标志物。此外，在小鼠NEC模型中，与人类NEC中差异表达的mirna相关的信号转导分子发生了改变，这表明该疾病的小鼠模型与实际的人类表现之间存在潜在的交叉。
Early-stage symptomology of necrotizing enterocolitis (NEC) is similar in presentation to non-NEC sepsis, though the treatment plans differ based on antibiotic administration and withholding of feeds. Improved diagnostics for NEC differentiation would allow clinicians to more rapidly set individual patients on a targeted treatment path. Extracellular vesicle-derived miRNAs, have previously demonstrated efficacy as disease biomarkers. To determine if these miRNAs are differentially-expressed in NEC infants, we performed transcriptomic analysis of urine-derived extracellular vesicle-derived miRNAs. Urine was non-invasively obtained from infants in one of four groups (n≥8) (Medical NEC, Surgical NEC, non-NEC sepsis, and healthy age-matched controls). EV-derived miRNAs were isolated and transcriptomic analysis was performed. Multiple miRNAs, including miR-376a, miR-518a-3p and miR-604, were significantly altered when comparing NEC to non-NEC sepsis and healthy controls, and could potentially be used as specific NEC biomarkers. Additionally, Ingenuity Pathway Analysis demonstrated that miRs differentially-expressed in NEC were associated with inflammatory disease and intestinal disease. Signal transduction molecules associated with NEC including TP53 and RPS15, which were also reduced transcriptionally in a rat model of NEC. These data indicate that there is a pool of potential urine EV-derived miRNAs that may be validated as NEC biomarkers in the differentiation of NEC from non-NEC sepsis and from age-matched controls. Additionally, signal transduction molecules associated with miRNAs differentially-expressed in human NEC are altered in a murine model of NEC, suggesting potential crossover between murine models of the disease and actual human presentation.
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影响因子：
16.6
作者：
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影响因子：
7.3
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通讯作者：
Inngjerdingen M
影响因子：
10.6
作者：
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影响因子：
5.4
作者：
Aubrey, Brandon J.;Strasser, Andreas;Kelly, Gemma L.
通讯作者：
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影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A