Treatable strategy for Dupuytren's disease using micro RNA technology

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K09574
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Mie University
• Principal Investigator: Tsujii Masaya 三重大学, 医学系研究科, リサーチアソシエイト (40444442)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: デュピュイトラン拘縮 / 筋線維芽細胞 / マイクロリボ核酸 / トロンビン

Outline of Final Research Achievements

Dupuytren’s Disease (DD) is a disease which cause permanent contracture of the fingers due to contraction of the palmar fascia. Although the pathophysiology is unclear, the myofibroblast is likely to play central roles in the progression of this disease. We aimed to determine expression of α-smooth muscle actin (αSMA), a marker of myofibroblast in the administration of thrombin and TGF-beta, and to analyze the effect of argatroban and antagmir-21 in the fibroblasts from the DD fascia including the nodules and the fibrous cords. The expression of αSMA was significantly upregulated by administration of thrombin and TGF-beta in the fibroblast from both nodules and cords of the DD fascia. In addition, the cell proliferation and migration were significantly increased by administration of thrombin and TGF-beta the fibroblasts from fibrous cord of DD. The administration of the argatroban and antagomir-21 significantly downregulated αSMA’s expression.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

本研究において、デュピュイトラン拘縮（Dupuytren’s disease: DD）の拘縮索においてmiR-21の高発現が示された。miR-21は発現の増大により病態に関与する特殊なマイクロRNAであることが示されている。また線維化促進因子であるthrombinの抑制により筋線維芽細胞分化の抑制が示され、同様にantagomir-21の投与も筋線維芽細胞への分化を抑制した。これらの投与がDDにおける細胞レベルでの新規の治療となる可能性が示された。