| Project/Area Number |
18K15798
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
Takano Keiko 東京慈恵会医科大学, 医学部, 助教 (00817207)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | AIH / PBC / miRNA / 自己免疫性肝炎 / 原発性胆汁性胆管炎 / PSC / 自己免疫性肝疾患 |
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| Outline of Final Research Achievements |
We performed a comprehensive expression analysis using miRNA microarrays focusing on the autoimmune liver diseases AIH and PBC. 28 AIH cases and 29 PBC cases were analyzed for miRNAs that could serve as screening indicators for diagnosis and disease assessment, such as disease activity and response to treatment. We found several miRNAs that varied significantly in each disease. In particular, four miRNAs (miR-3196, miR-6125, miR-4725-3 p and miR-4634) were identified that were highly elevated in AIH and could clearly diagnose AIH and PBC with high sensitivity and specificity. In situ hybridization showed that the localization of these miRNAs was moderately to highly expressed in the hepatocyte cytoplasm of AIH patients. Furthermore, steroid treatment reduced the levels of these miRNAs, which correlated histologically with sever hepatic necroinflammatory activity. Therefore, the identified miRNAs were suggested to be potential diagnostic and disease assessment biomarkers for AIH.
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| Academic Significance and Societal Importance of the Research Achievements |
自己免疫性肝疾患は総じて難治性かつ進行性の希少疾患である。miRNAはタンパクをコードしない小分子RNAで、mRNAへの翻訳抑制作用により様々な生命現象を制御している。近年、miRNAは機能的分泌や細胞破壊による遊離により血液中に放出され、その発現プロファイルは疾患やその病態毎に異なることが報告されており、早期診断や疾患進展・治療反応性マーカーとしての臨床応用が期待されている。本研究における我々の研究成果により同定されたAIH高値となるmiRNAsは、AIHの診断および病勢評価バイオマーカーとなる可能性を示しており、有益な発見であると考える。
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