Development of a method to predict the severity of nonalcoholic fatty liver disease by exosomal microRNA

• Project/Area Number: 17K08984
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Kagawa University
• Principal Investigator: Yoneyama Hirohito 香川大学, 医学部附属病院, 助教 (80294750)
• Co-Investigator(Kenkyū-buntansha): 正木 勉 香川大学, 医学部, 教授 (30335848)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 非アルコール性脂肪性肝疾患 / NAFLD / 非アルコール性脂肪肝炎 / NASH / マイクロRNA / 予後予測 / エクソソーム / 体組成 / 予後予測式 / 臨床 / 内科 / マイクロアレイ

Outline of Final Research Achievements

For the purpose of identifying biomarkers useful for prognosis of NAFLD, exosomal microRNA (exo-miRNA) was extracted from the serum of patients, and comprehensive analysis was carried out using oligo chips loaded with thousands of miRNAs. As a result, several exo-miRNAs that correlate with NASH development were identified. However, when these were quantified by RT-PCR and their correlation with NAFLD severity was examined, no significant correlation was shown. Analysis of the cause revealed that the patient's body composition profile was heterogeneous. It has been speculated that body composition is deeply involved in the development of NASH. Therefore, we are currently analyzing exo-miRNAs by body composition type to identify exo-miRNAs involved in NASH development.

Academic Significance and Societal Importance of the Research Achievements

NASH/NAFLD 研究を困難にしている最大要因の１つは患者背景の多様性であるが、今回の研究成果から血清エクソソームマイクロRNA（exo-miRNA） 解析と体組成計測の2つが多様な患者背景を重症化予測の観点から明確に分類できる可能性が示唆された。本研究の更なる進展が膨大なNAFLD患者から肝硬変・肝発がんに進展するNASH を効率的にスクリーニングする新たな診断技術開発につながると考えている。

Research Products

• [Presentation] 生体電気インピーダンス法を用いた体組成計測によるNAFLD/NASHの肝線維化進展および治療効果予測 (2019)
  • Author(s): 米山弘人、森下朝洋、谷丈二、野村貴子、坂本鉄平、藤田浩二、田所智子、大浦杏子、中原麻衣、琢磨慧、出口章広、樋本尚志、正木勉
  • Organizer: 第４３回日本肝臓学会西部会
• [Presentation] Assessment of the progression of liver fibrosis by body comparison analysis by bioelectrical impedance analysis (2019)
  • Author(s): Hirohito Yoneyama, Asahiro Morishita , Joji Tani, Takako Nomura, Teppei Sakamoto, Koji Fujita, Shima Mimura, Tomoko Tadokoro, Kyoko Oura, Mai Nakahara, Kei Takuma, Akihiro Deguchi, Takashi Himoto, Tsutomu MASAKI
  • Organizer: APASL STC 2019 TOKYO
  • Int'l Joint Research
• [Presentation] Assessment of the progression of liver fibrosis by body comparison analysis by bioelectrical impedance analysis (2019)
  • Author(s): Hirohito Yoneyama, Asahiro Morishita, Takako Nomura, Teppei Sakamoto, Koji Fujita, Shima, Mimura, Tomoko Tadokoro, Kyoko Oura, Mai Nakahara, Kei Takuma, Joji Tani, Akihiro Deguchi, Takashi Himoto, Tsutomu Masaki
  • Organizer: The Asian Pacific Association for the Study of the Liver
  • Int'l Joint Research