2021 Fiscal Year Final Research Report
Molecular mechanisms underlying circadian pruritic behavior for chronopharmacology
| Project/Area Number |
19K16371
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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 47040:Pharmacology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 体内時計 / 発現制御機構 / 翻訳 |
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| Outline of Final Research Achievements |
In the course of elucidating the molecular mechanisms underlying circadian pruritic behavior for chronopharmacology, we found that the N-type glycosylation of Gpr176, an orphan GPCR that sets the pace of the circadian clock, plays an important role in the regulation of its protein expression level (Wang and Nakagawa et al, Sci Rep, 2020), developed a system that enables us to observe a number of circadian rhythms in physiology simultaneously (Shimatani et al, PLoS ONE, 2021), and found that in meibomian gland dysfunction, in which local changes in peripheral organs are associated with the development of its pathogenesis like itch, an age-related decrease in NAD+ leads to a decrease in local steroid synthesis, which result in an exacerbation of the disease (Sasaki, Hamada, and Yarimizu et al, Nat Aging, 2022).
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| Free Research Field |
生化学
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| Academic Significance and Societal Importance of the Research Achievements |
これまでかゆみをはじめとした末梢器官の機能異常が引き金となる疾患に関する多くの研究では、末梢器官に発現する分子に焦点を当てるものが多く、そこに時間の概念は無かった.生体内の時間を形成する体内時計の制御機構に関しては、体内時計コア遺伝子mRNAの発現リズム調節を介した機構がこれまで明らかになってきたが、非転写型の調節機構にはまだ未解明な部分が残されている. そのような中本研究では、体内時計制御分子の発現量が翻訳後修飾によって制御されること、眼瞼における低分子NAD+量の概日振動がマイボーム腺機能の維持に重要であることを見出した. 時間薬理学を行う上での重要な基礎を築くことができたといえる.
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