Role of Nrf2 signaling in development of hepatocyte like cells
| Project/Area Number |
19K09094
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TAKASU Chie 徳島大学, 大学院医歯薬学研究部(医学域), 講師 (70582823)
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| Co-Investigator(Kenkyū-buntansha) |
齋藤 裕 徳島大学, 病院, 講師 (50548675)
森根 裕二 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (60398021)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | heparocyte like cell / ADSC / Nrf2 / HCLC |
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| Outline of Research at the Start |
Dimethyl Fumarate(DMF)ストレス応答転写因子NF-E2 related factor 2(Nrf2)のinducerとして知られており、我々はすでに肝虚血再灌流（Takasu C. World J Gastroenterol. 2017）、薬剤性腎症モデル（Takasu C. Transplantation. 2015）において保護作用を有することを報告している。一方で、Nrf2を過剰発現した間葉系幹細胞（MSC）は骨芽細胞への分化誘導が促進される（Biochem Biophys Res Commun. 2017）ことが知れており、MSCを用いた再生研究においてNrf2が治療標的になる可能性が考えらえる。本研究では、DMFによるNfr2を介したMSCの分化を検討し、より効率的にMSCからhepatocyte-like cellへの分化誘導可能なプロトコールを確立する。
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| Outline of Final Research Achievements |
The generation of hepatocytes derived from human adipose-derived mesenchymal stem cells (ADSCs) could be a promising source of alternative human hepatocytes. As Nrf2 signaling showed protective role in liver regeneration, we investigated the role of Nrf2 in differentiation of hepatocyte-like cells (HLCs).
The nucleus translocation of Nrf2 was significantly occurred since day 11 through the progression of differentiation of HLCs. The nucleus translocation of Nrf2 in GSK3 inhibitor treated group was obviously higher than the other groups at day 11 (step 2). Moreover, the nucleus translocation of Nrf2 in GSK3 inhibitor treated group was notably higher than other groups in step 3. Luciferin-IPA Activity of GSK3 inhibitor treated group was higher than other 3 groups. Nrf2 was activated in during the procedure of HLCs differentiation step. Nrf2 might be a notable target in developing high functional human HLCs.
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| Academic Significance and Societal Importance of the Research Achievements |
今回GSK3阻害剤によるNrf2の核内移行はHLC機能の向上に寄与していると考えられた。MSCからHLCへの分化誘導の過程において、Nrf2活性化によりHLCへの分化効率が上昇すれば、低侵襲かつ迅速に移植が可能となり、画期的な治療につながり得ると考えられる。肝移植における慢性的ドナー不足を考慮すると、機能的肝細胞を倫理上の問題なく安全に確保できる手法の開発の恩恵は計り知れないと考えられる。
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Report
(4 results)
Research Products
(1 results)
