Bile extracellular vesicles from end-stage liver disease patients show altered microRNA content
Bile extracellular vesicles from end-stage liver disease patients show altered microRNA content
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DOI：
10.1007/s12072-021-10196-5
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发表时间：
2021-02
影响因子：
6.6
通讯作者：
Suguru Nakashiki;S. Miuma;H. Mishima;H. Masumoto;M. Hidaka;A. Soyama;Yasuko Kanda;Masanori Fukushima;Masafumi Haraguchi;R. Sasaki;H. Miyaaki;T. Ichikawa;M. Takatsuki;S. Eguchi;K. Yoshiura;K. Nakao
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作者：
Suguru Nakashiki;S. Miuma;H. Mishima;H. Masumoto;M. Hidaka;A. Soyama;Yasuko Kanda;Masanori Fukushima;Masafumi Haraguchi;R. Sasaki;H. Miyaaki;T. Ichikawa;M. Takatsuki;S. Eguchi;K. Yoshiura;K. Nakao
背景细胞外囊泡（Extracellular vesicles，EVs）作为一种新型的诊断生物标志物和治疗工具，近年来引起了人们的广泛关注.一些报告将血液EV与肝脏疾病相关联。然而，血液EV不反映肝脏状态，因为它包含其他全身循环EV。因此，我们专注于胆汁EV，这是直接从肝脏分泌，为识别潜在的生物标志物的肝failure.MethodsBile样本收集自肝移植受者（n= 21）诊断为终末期肝病（ESLD）和捐助者（正常肝脏，NL;n= 18）在移植过程中。胆汁EV提取使用ultracentrication.ResultsNanoparticle跟踪分析表明，胆汁EV浓度显着高于受体比捐助者。在接受者中，胆汁EV浓度在肝细胞癌患者中显著较高。下一代测序显示，供体和受体胆汁EV中分别有461种和465种microRNA（miRNAs），两组之间的多样性没有显著差异。在43个高表达的miRNAs中，86.0%的miRNAs在受体胆汁EV中的表达高于供体。定量PCR验证显示，受体胆汁EV中miR-17、miR-92 a、miR-25、miR-423和miR-451 a的水平显著增加。酒精性ESLD受者的miR-17水平显着升高。结论ESLD状态下EV向胆汁中的分泌及其miRNA含量增加。此外，胆汁EV中的miRNA水平与血清EV中的miRNA水平不相关。胆汁EV可能是肝脏疾病的有前途的新生物标志物。
BackgroundExtracellular vesicles (EVs) have recently attracted attention as novel diagnostic biomarkers and therapeutic tools. Several reports have correlated blood EVs with liver diseases. However, blood EVs do not reflect the liver state as it contains other systemically circulating EVs. Therefore, we focused on bile EVs, which are secreted directly from the liver, for the identification of potential biomarkers of liver failure.MethodsBile samples were collected from liver transplant recipients (n= 21) diagnosed with end-stage liver disease (ESLD) and donors (normal liver, NL;n= 18) during transplantation. Bile EVs were extracted using ultracentrifugation.ResultsNanoparticle tracking analysis showed that bile EV concentration was significantly higher in recipients than in donors. Among recipients, bile EV concentration was remarkably higher in those with hepatocellular carcinoma. Next-generation sequencing revealed 461 and 465 types of microRNAs (miRNAs) in donor and recipient bile EVs, respectively, with no significant difference in diversity between the groups. Among 43 high-expression miRNAs, the expression of 86.0% of the miRNAs was higher in the bile EVs of recipients than in those of donors. Quantitative PCR validation showed that the levels of miR-17, miR-92a, miR-25, miR-423, and miR-451a significantly increased in bile EVs of recipients. Levels of miR-17 were remarkably higher in recipients with alcoholic ESLD.ConclusionsSecretion of EVs into the bile and their miRNA content increase in the ESLD state. Additionally, miRNA levels in bile EVs are not correlated with those in serum EVs. Bile EVs could be promising novel biomarkers for liver diseases.