Atypical GPCR signaling regulated by cysteine-based post-translational modification and its physiological significance
| Project/Area Number |
18K14921
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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 | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | プリン作動性受容体 / inflammation / 慢性炎症 / プリン受容体 |
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| Outline of Final Research Achievements |
We found that Iberine and sulforaphane, which are isothiocyanates (ITCs) contained in foods, inhibit P2Y6R signaling. Furthermore, ITCs induced internalization of P2Y6R and degradation via the proteasome system. ITCs-induced internalization and degradation of P2Y6R are caused by the 220th cysteine modification. In addition, in the DSS colitis model, which is an ulcerative colitis model, we found that deficient of P2Y6R attenuates body weight loss, disease activity index and the amount of inflammatory cytokine.
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| Academic Significance and Societal Importance of the Research Achievements |
クローン病や潰瘍性大腸炎に代表される炎症性腸疾患（以下IBD）は寛解と再燃を繰り返す腸管の慢性炎症を特徴とする難治性の疾患である。一方で、P2Y6Rは細胞外UDPをリガンドとするプリン作動性受容体であり、心臓や神経、免疫系細胞に発現している。本研究では過剰なP2Y6受容体の発現によるシグナルの増加が病態を進行させる可能性が示された。さらに、IBDの環境要因のうち食事に着目し、P2Y6受容体シグナリングを抑制する食事成分を見出した。本研究の成果により、大腸炎の発症メカニズムにおけるP2Y6Rの役割が明らかとなり、P2Y6Rを標的とした革新的な医療基盤技術の創出に発展させることが期待できる。
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Report
(3 results)
Research Products
(18 results)
