Mechanisms of TGF-beta induced treatment resistance in chronic rhinosinusitis.

2021 Fiscal Year Final Research Report

• 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: Yoshikawa Mamoru 東邦大学, 医学部, 教授 (50277092)
• Project Period (FY): 2018-04-01 – 2022-03-31
• 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.

Free Research Field

耳鼻咽喉科学

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。