2022 Fiscal Year Final Research Report
Do sirtuins contribute to the anti-inflammatory effects of ghrelin?
Project/Area Number |
20K08348
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Hokkaido University |
Principal Investigator |
Takeda Hiroshi 北海道大学, 薬学研究院, 名誉教授 (60261294)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | グレリン / サーチュイン |
Outline of Final Research Achievements |
I investigated the possibility that ghrelin receptor stimulation exerts anti-inflammatory effects through activation of intracellular SIRT1 and/or SIRT3. In HEK293 cells stably expressing the ghrelin receptor, SIRT1 mRNA and protein levels were significantly increased after addition of ghrelin. SIRT3 mRNA transiently decreased and then increased, and the SIRT3 protein level tended to increase. Furthermore, acetylation of mitochondria-localized p53 was decreased upon ghrelin stimulation. These results suggested that ghrelin receptor stimulation activated cytoplasmic SIRT1 localized near mitochondria. Furthermore, PGC-1α, NRF-1, and TFAM mRNAs, were increased after ghrelin addition, suggesting that mitochondrial biogenesis was also promoted.
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Free Research Field |
消化器内科学
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Academic Significance and Societal Importance of the Research Achievements |
グレリンは、グレリン受容体を介して細胞内SIRT1/3を活性化し、ミトコンドリア新生を促進する可能性が示された。これらは、グレリンによる抗炎症作用の一部である可能性が高いと考えられる。この点がさらに明らかとなり、さらに慢性炎症状態におけるグレリン抵抗性の機序を解明することができれば、慢性炎症性疾患における炎症の持続機構の解明、ならび同機構の解除を目指す新規治療の開発につなが ることが期待される。
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