| Budget Amount *help |
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
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| 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.
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