2022 Fiscal Year Final Research Report
Molecular basis of the regulation of intestinal cellular lifespan
| Project/Area Number |
20K07358
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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 49010:Pathological biochemistry-related
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 腸上皮細胞 / 細胞寿命 / mTORC1 / Tsc2 / Ras / CD47 |
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| Outline of Final Research Achievements |
Intestinal epithelial cells (IECs) are continuously regenerated from Lgr5-positive intestinal stem cells (ISCs). The life-span of matured IECs is relatively short, and its proper regulation is important for maintaining homeostasis of intestine. In this study, we found that the downstream molecules of receptor protein kinases such as mTORC1 and Ras inhibited Wnt signaling pathway which was important for maintaining the stemness of ISCs, and reduced the number of Lgr5-positive ISCs. We believe that cross-talk between mTORC1or Ras and Wnt signaling pathway is important not only for proper regulation of IEC homeostasis but for the development of intestinal diseases and potentially for their therapy.
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| Free Research Field |
生化学・分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
腸上皮細胞の寿命制御メカニズムについて理解することを目的とした本研究の成果は、学術的に未解決な問題である「細胞寿命の制御機構の解明」に寄与する。一方で近年、食の欧米化に伴って我が国でも増加傾向のある炎症性腸疾患や大腸がんなどの発症機構の理解にも本研究の成果は寄与する。そのため本研究の成果はこれらの腸疾患の診断法や治療法を開発する上で有力な情報を提供することが想定される。
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