Elucidation of the pathophysiology of secondary lymphedema and development of new drug treatments

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08789
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Sano Masaki 浜松医科大学, 医学部附属病院, 助教 (40733514)
• Co-Investigator(Kenkyū-buntansha): 横山 由里奈 浜松医科大学, 医学部附属病院, 理学療法士 (30645875) ; 片橋 一人 浜松医科大学, 医学部附属病院, 診療助教 (60839091)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: リンパ浮腫 / 皮膚線維化 / TGF-β / 脂肪細胞 / エイコサペンタエン酸

Outline of Final Research Achievements

We showed the pathophysiology of secondary lymphedema using a rat model. Macrophages in the acute phase, myofibroblasts and macrophages in increased adipose tissue in the chronic phase were important. TGF-β1 was produced from these cells, and caused skin fibrosis via SMAD signals. Lymphatic vessels were impaired in fibrotic skin tissue. Eicosapentaenoic acid (EPA) inhibited increase of adipocytes and TGF-β1 signaling, and improved skin fibrosis. Lymphatic function was also improved. Fibroblasts were obtained from skin samples of rat model and patients with secondary lymphedema. These fibroblasts were differentiated into myofibroblasts. Addition of EPA to cultured myofibroblasts inhibited the expression of TGF-β1 and collagen.

Free Research Field

血管外科

Academic Significance and Societal Importance of the Research Achievements

子宮がんや乳がんなど、リンパ節郭清を伴う悪性腫瘍手術後に四肢リンパ浮腫が発症する。四肢体積は増加し、慢性期には皮膚が硬くなり、生活の質（QOL）は著しく障害される。しかし、マッサージや弾性着衣での圧迫など理学療法が中心で、有効な薬物治療はない。本研究は、リンパ浮腫の病態を解明し、新しい薬物治療の可能性を示した。今後の臨床研究、新しい薬物治療の開発への橋渡しになる研究である。