Identification of microRNA biomarker candidates in urine and plasma from rats with kidney or liver damage.
Identification of microRNA biomarker candidates in urine and plasma from rats with kidney or liver damage.
复制标题
DOI：
10.1002/jat.3358
复制
发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Kirby PJ
中科院分区：
文献类型：
--
作者：
Wolenski FS;Shah P;Sano T;Shinozawa T;Bernard H;Gallacher MJ;Wyllie SD;Varrone G;Cicia LA;Carsillo ME;Fisher CD;Ottinger SE;Koenig E;Kirby PJ
MicroRNAs(MiRNA)是一种短的单链RNA序列，在基因的转录后调控中发挥作用。鉴定组织特异性或富集型miRNAs作为新的安全生物标志物具有很大的潜力。一个长期的目标是将生物体液(例如血浆和尿液)中miRNA的增加与组织特异性损伤联系起来。下一代测序(miR-seq)用于分析肾毒性药物(顺铂)或两种肝毒性药物之一(对乙酰氨基酚[APAP]或四氯化碳[CCl4])处理的大鼠组织、血浆和尿样miRNA图谱的变化。传统的血清化学和组织病理学分析证实，毒物引起的器官损伤具有特异性。在接受顺铂治疗的动物中，肾脏中有5个miRNAs的水平发生了显著变化，血浆中有14个，尿中有6个。在APAP处理的动物中，肝脏中有5个miRNAs发生了变化，血浆中有74个miRNAs发生了变化，尿中有6个miRNAs发生了变化；对于CCl4，这些变化分别为5个、20个和6个。顺铂治疗导致尿中miR-378a升高，证实了其他类似研究的结果。经APAP或CCl4处理后，血浆中常见的miRNAs有17个升高。其中四种化合物(miR-122、−802、−31a和−365)已知在大鼠的肝脏中富含。有趣的是，两种肝毒治疗中血清miR-802的升高与众所周知的肝损伤标记物miR-122相当。总之，对尿液和血浆miRNAs的比较分析表明，它们作为器官损伤的生物标志物是有用的。版权所有(C)2016作者。应用毒理学杂志由John Wiley&Sons有限公司出版。microRNAs(MiRNA)作为新的安全生物标志物具有巨大的潜力。下一代测序用于分析肾毒物(顺铂)或两种肝脏毒物之一(扑热息痛或四氯化碳)处理的大鼠组织、血浆和尿样miRNA图谱的变化。顺铂治疗导致尿中miR-378a升高，证实了其他类似研究的结果。用对乙酰氨基酚或四氯化碳治疗后，血清中四种富含肝脏的−(miR-122、miR802、−31a和−365)水平升高。
MicroRNAs (miRNA) are short single‐stranded RNA sequences that have a role in the post‐transcriptional regulation of genes. The identification of tissue specific or enriched miRNAs has great potential as novel safety biomarkers. One longstanding goal is to associate the increase of miRNA in biofluids (e.g., plasma and urine) with tissue‐specific damage. Next‐generation sequencing (miR‐seq) was used to analyze changes in miRNA profiles of tissue, plasma and urine samples of rats treated with either a nephrotoxicant (cisplatin) or one of two hepatotoxicants (acetaminophen [APAP] or carbon tetrachloride [CCL4]). Analyses with traditional serum chemistry and histopathology confirmed that toxicant‐induced organ damage was specific. In animals treated with cisplatin, levels of five miRNAs were significantly altered in the kidney, 14 in plasma and six in urine. In APAP‐treated animals, five miRNAs were altered in the liver, 74 in plasma and six in urine; for CCL4 the changes were five, 20 and 6, respectively. Cisplatin treatment caused an elevation of miR‐378a in the urine, confirming the findings of other similar studies. There were 17 in common miRNAs elevated in the plasma after treatment with either APAP or CCL4. Four of these (miR‐122, −802, −31a and −365) are known to be enriched in the livers of rats. Interestingly, the increase of serum miR‐802 in both hepatotoxicant treatments was comparable to that of the well‐known liver damage marker miR‐122. Taken together, comparative analysis of urine and plasma miRNAs demonstrated their utility as biomarkers of organ injury. Copyright © 2016 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. MicroRNAs (miRNA) have great potential as novel safety biomarkers. Next‐generation sequencing was used to analyze changes in miRNA profiles of tissue, plasma and urine samples of rats treated with either a nephrotoxicant (cisplatin) or one of two hepatotoxicants (acetaminophen or carbon tetrachloride). Cisplatin treatment caused an elevation of miR‐378a in the urine, confirming the findings of other similar studies. Treatment with either acetaminophen or carbon tetrachloride caused a serum elevation of four liver‐enriched miRNAs (miR‐122, −802, −31a and −365).