2022 Fiscal Year Final Research Report
Mechanism of TSLP suppression by hypoxia signal-induced epigenetic gene regulation
| Project/Area Number |
21K15252
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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 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Keywords | 低酸素 / HIF / TSLP / アトピー性皮膚炎 / ケラチノサイト / JNK / PHD 阻害薬 |
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| Outline of Final Research Achievements |
In this study, we aimed to elucidate the mechanism by which PHD inhibitors suppress TSLP expression. PHD inhibitors induce DUSP protein expressions through HIF and HDAC activation in a human keratinocyte cell line. Induction of DUSP expression suppresses JNK/AP-1 signaling that contributes to TSLP expression. In addition, we found that PHD inhibitors inhibited TSLP production in a mouse allergic sensitization model. From these findings, we have clarified the anti-allergic effect of PHD inhibitors and its detail mechanisms of action.
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| Free Research Field |
皮膚免疫
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は皮膚の表皮の恒常性維持に重要な HIF の活性化がアレルギー性免疫応答の誘導因子である TSLP 発現を抑制する機序を解明した。これは皮膚の持つ免疫制御機構の理解につながる。また、HIF の活性化を誘導する PHD 阻害薬がアレルゲン感作を抑制する作用を持つことを明らかにしており、PHD 阻害薬のアレルギー治療への応用性を示唆できた。これにより、既に腎性貧血に対して臨床応用されている PHD 阻害薬の新たな治療応用への展開が期待できる。
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