Long Noncoding RNAs in Urine Are Detectable and May Enable Early Detection of Acute T Cell-Mediated Rejection of Renal Allografts
Long Noncoding RNAs in Urine Are Detectable and May Enable Early Detection of Acute T Cell-Mediated Rejection of Renal Allografts
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DOI：
10.1373/clinchem.2015.243600
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发表时间：
2015-12-01
影响因子：
9.3
通讯作者：
Thuml, Thomas
中科院分区：
文献类型：
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作者：
Lorenzen, Johan M.;Schauerte, Celina;Thuml, Thomas
背景：长链非编码rna （lncRNAs）是调控基因组和蛋白质组的新型细胞内非编码核糖核苷酸。它们可以在急性肾损伤患者的血液中检测到。我们测试了lncrna是否存在于尿液中，并可能作为肾移植急性排斥患者预后的新预测因子。方法：利用急性T细胞介导的肾移植排斥反应患者和对照移植患者尿液中的RNA进行全球lncRNA表达分析。在62例急性排斥反应患者（其中10例在抗排斥治疗成功后）和31例对照移植患者的肾脏活检和尿液中证实了lncrna的失调。结果：一项全球筛查显示，急性排斥患者的尿液中有几种lncrna失调。三个基因间lncRNAs， LNC-MYH13-3:1, RP11-395P13.3-001和RP11-354P17.15-001，发生了最强烈的改变。这些在整个患者队列中得到了验证。与对照组相比，急性排斥反应患者中RP11-395P13.3-001和RP11-354P17.15-001表达上调。在抗排斥治疗成功的急性排斥患者中，只有RP11-354P17.15-001水平恢复正常。RP11-354P17.15-001与移植后1年肾小球滤过率的较高下降相关。体外，在小管上皮细胞中，经白细胞介素-6处理后，所有lncRNAs均富集，但细胞培养上清中只有RP11-395P13.3-001和RP11-354P17.15-001增加，说明这些lncRNAs可能在炎症条件下分泌。结论：急性排斥反应患者尿液中lncrna发生强烈改变。尿RP11-354P17.15-001可能作为急性肾排斥反应的一种新的生物标志物，用于识别急性排斥反应患者和预测肾功能丧失。(C) 2015美国临床化学协会
BACKGROUND: Long noncoding RNAs (lncRNAs) are novel intracellular noncoding ribonucleotides regulating the genome and proteome. They are detectable in the blood of patients with acute kidney injury. We tested whether lncRNAs are present in urine and may serve as new predictors of outcome in renal transplant patients with acute rejection.METHODS: A global lncRNA expression analysis was performed with RNA from urine of patients with acute T cell mediated renal allograft rejection and control transplant patients. Deregulated lncRNAs were confirmed in kidney biopsies and urine in a validation cohort of 62 patients with acute rejection, 10 of them after successful antirejection therapy, and 31 control transplant patients.RESULTS: A global screen revealed several lncRNAs to be deregulated in urine of patients with acute rejection. Three intergenic lncRNAs, LNC-MYH13-3:1, RP11-395P13.3-001, and RP11-354P17.15-001, were most strongly altered. These were validated in the whole cohort of patients. RP11-395P13.3-001 and RP11-354P17.15-001 were up-regulated in patients with acute rejection compared with controls. Only levels of RP11-354P17.15-001 normalized in patients with acute rejection after successful antirejection therapy. RP11-354P17.15-001 was associated with higher decline in glomerular filtration rate 1 year after transplantation. In vitro, in tubular epithelial cells, all lncRNAs were enriched by interleukin-6 treatment, but only RP11-395P13.3-001 and RP11-354P17.15-001 increased in cell culture supernatant, indicating that these lncRNAs might be secreted under inflammatory conditions.CONCLUSIONS: lncRNAs are strongly altered in urine of patients with acute rejection. Urinary RP11-354P17.15-001 may serve as a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function. (C) 2015 American Association for Clinical Chemistry