Alternative Title末期肝不全患者において胆汁中細胞外小胞の内包microRNAは変化する
Degree grantor/typeNagasaki University (長崎大学)
Note (General)Background: Extracellular 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.Methods: Bile 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.Results: Nanoparticle 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.Conclusions: Secretion 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.
長崎大学学位論文 学位記番号:博(医歯薬)甲第1362号 学位授与年月日:令和3年9月1日
Author: Suguru Nakashiki, Satoshi Miuma, Hiroyuki Mishima, Hiroshi Masumoto, Masaaki Hidaka, Akihiko Soyama, Yasuko Kanda, Masanori Fukushima, Masafumi Haraguchi, Ryu Sasaki, Hisamitsu Miyaaki, Tatsuki Ichikawa, Mitsuhisa Takatsuki, Susumu Eguchi, Koh-ichiro Yoshiura & Kazuhiko Nakao
Citation: Hepatology International; 15(3), pp. 821–830; 2021
identifier:Nagasaki University (長崎大学), 博士(医学) (2021-09-01)
http://hdl.handle.net/10069/00040949
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2022-06-05T18:01:14+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション