2018 Fiscal Year Final Research Report
Elucidation of "Dying Code" for liver stem/progenitor cell-mediated regeneration
| Project Area | Homeostatic Regulation by Various Types of Cell Death |
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| Project/Area Number |
26110007
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
TANAKA MINORU 国立研究開発法人国立国際医療研究センター, その他部局等, 細胞療法開発研究室長 (80321909)
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| Research Collaborator |
Matsuda Michitaka
Matsui Satoshi
Miura Yasushi
Tsurusaki Shinya
Kimura Takuya
Nagashima Yuri
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| Project Period (FY) |
2014-07-10 – 2019-03-31
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| Keywords | 細胞死 / 肝炎 / 肝線維化 / 肝再生 / 肝前駆細胞 |
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| Outline of Final Research Achievements |
Our aim is to clarify the role and significance of cell death in the process of liver regeneration or fibrosis in the liver diseases. Consequently, we have succeeded in the identification of two novel factors related to cell death, which are involved in the regulation of liver regeneration and fibrosis, respectively. In addition, we revealed their regulatory mechanisms in liver regeneration and fibrosis based on the cell-cell interaction. Especially, we found that bone marrow derived macrophages plays an important role in the progression of liver fibrosis. On the other hand, we have developed the genetically manipulated mice capable of labeling the liver progenitor cells (LPCs) to monitor the liver regeneration mediated by LPCs in vivo. Furthermore, we discovered that ferroptosis plays a crucial role in the pathogenesis of non-alcoholic steatohepatitis (NASH) by cooperating with several units in this research group “Dying Code”.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
我々の研究から、近年社会問題化しつつある非アルコール性脂肪性肝炎(NASH)の発症過程において、単純性脂肪肝から肝炎への移行にフェロトーシスという細胞死が関わることが明らかとなった。今後、フェロトーシスの分子メカニズムをさらに解明することでNASHの予防法や治療法の開発につながることが期待される。また、肝マクロファージが肝星細胞間との相互作用を介して肝線維化を誘導していることが判明した。肝臓が線維化に至るメカニズムの一端が明らかとなったことから、新規の治療法の開発につながることが期待される。
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