Macrophage Foam Cell Formation Induced by the Peptide Derived from Tenascin-C
| Project/Area Number |
15K19034
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
IYODA Takuya 東京理科大学, 薬学部生命創薬科学科, 講師 (80465715)
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| Research Collaborator |
FUKAI Fumio 東京理科大学, 薬学部・生命創薬科学科, 教授 (90124487)
NAKAGAWA Yoshimi 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80361351)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | テネイシンC / 細胞外マトリックス / マクロファージ / 動脈硬化 / 炎症 / 動脈硬化病態形成 / インテグリン / 泡沫化 / ABCA1 / ABCG1 |
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| Outline of Final Research Achievements |
Tenascin-C (TNC) is known to be upregulated in inflammation including atherosclerosis. Previously, we found a bioactive region termed TNIIIA2 from TNC, and the exposure of this region might be mediated through digestion of TNC by inflammatory proteases. Since macrophages are accumulated in inflammatory site, we hypothesized that the pro-atherosclerotic activity of macrophages might be modulated by TNIIIA2.
In this study, we showed the possibility that TNIIIA2 would contribute to the progression of atherosclerosis through acceleration of foam cell formation. It would be promoted by enhanced phagocytosis, and suppressed cholesterol efflux through down-regulation of ABCA1/G1. We also observed that the reagent, which could cancel TNIIIA2-mediated b1-integrin activation, could inhibit atherosclerotic plaque formation in LDLR-KO mice. Taken together, TNIIIA2 might be a key player in atherosclerosis progression and become a good candidate for a new target of anti-atherosclerosis treatment.
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Report
(3 results)
Research Products
(9 results)
