Analysis of the effects of high-density environment on fibroblasts in rheumatoid arthritis and its prospects for therapeutic application

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16301
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Yamamoto Akio 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座助教 (10845366)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 関節リウマチ / 滑膜線維芽細胞 / YAP/TAZ / 細胞密度

Outline of Final Research Achievements

The importance of YAP/TAZ and TEAD in synovial fibroblasts in rheumatoid arthritis has been demonstrated. These molecules are known to regulate important functions in rheumatoid arthritis fibroblast function such as cell proliferation, survival, and migration. RNA sequencing was performed on rheumatoid arthritis synovial fibroblasts with TEAD inhibitors. As a result, we tried to identify important molecules that may be affected by TEAD inhibitors. Some of these molecules may play important roles in the pathogenesis of rheumatoid arthritis. We further evaluated the role of these molecules using WB, immunocytochemistry, siRNA-based knockdown, and inhibitor administration.

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Free Research Field

膠原病・関節リウマチ

Academic Significance and Societal Importance of the Research Achievements

関節リウマチの病態において滑膜組織の線維芽細胞は重要な役割を果たしています。本研究では細胞の密度が高いかどうかを制御することに重要なYAP/TAZとTEADという分子が、関節リウマチの滑膜線維芽細胞の増殖などの働きに重要で、それを抑制することが関節リウマチの病態制御に有効である可能性を検証しました。将来的な滑膜線維芽細胞の病態の理解、治療に貢献できる可能性があります。