| Project/Area Number |
18K09329
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 56050:Otorhinolaryngology-related
|
|---|
| Research Institution | Toho University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | 慢性副鼻腔炎 / エンドタイプ / TGF-β / エピジェネティクス / 線維芽細胞 |
|---|
| Outline of Final Research Achievements |
Although it is recently possible to control the disease in many cases of chronic rhinosinusitis, there are still a small number of refractory cases who repeatedly relapse despite surgery and topical steroid administration. In such cases, eosinophilia in the peripheral blood and nasal tissues is often absent, suggesting the presence of refractory factors other than eosinophils.
Therefore, we conducted this study to elucidate a novel mechanisms of refractoriness of chronic rhinosinusitis, and found that TGF-β-dependent endotypes are often involved in refractory cases. However, no epigenetics induced by TGF-β was observed in fibroblasts derived from nasal tissue, as initially expected.
|
| Academic Significance and Societal Importance of the Research Achievements |
慢性副鼻腔炎におけるTGF-β依存性エンドタイプの同定により、新たな治療抵抗性の病態の存在を明らかにしたものの、TGF-βによって誘導される線維芽細胞のエピジェネティックな変化が慢性副鼻腔炎の難治化に関わる新たな機序であることは証明できなかった。
しかし、慢性副鼻腔炎患者の鼻組織由来の線維芽細胞において広範なDNAメチル化の変動を確認し、特にペリオスチン遺伝子のプロモーター領域に低メチル化を認めたことから、このメカニズムの解明により、既存の治療に抵抗性の病態に対する新規治療の開発や創薬に繋がる可能性が示唆された。
|
