Creation of a novel animal model of secondary lymphedema and development of the therapy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293310
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Naoki Unno 浜松医科大学, 医学部, 准教授 (20291958)
• Co-Investigator(Kenkyū-buntansha): 山本 尚人 浜松医科大学, 医学部附属病院, 助教 (80402262)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: リンパ浮腫 / 動物モデル / TGF-β / 線維化 / 筋線維芽細胞 / 治療 / Eicosapentaenoic acid

Outline of Final Research Achievements

The pathophysiology of secondary lymphedema remains unclear . Lack of an animal model has hindered investigations on the pathophysiology of the disease. We developed a novel animal model of secondary lymphedema using the rat hindlimb. Then, we identified that transforming growth factor (TGF)-β1 was produced by macrophages in the acute phase and by fibroblasts in the late phase of the disease. Further, TGF-β1 was observed to differentiate fibroblasts to myofibroblasts, accelerating collagen synthesis to result in fibrosis. Eicosapentaenoic acid (EPA) inhibited myofibroblasts producing TGF-β1 in skin samples harvested from the hindlimbs of our animal models, as well as from the legs of patients with secondary lymphedema. Moreover, daily administration of EPA effectively inhibited fibrosis in our rat model via suppression of TGF-β1. We showed EPA inhibits fibrosis in secondary lymphedema via suppression of myofibroblasts producing TGF-β1.

Free Research Field

血管外科学