Mechanism of adipose angiogenesis by the cooperative action of angiogenic factors
Project/Area Number |
18K08469
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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Research Institution | University of Toyama |
Principal Investigator |
Wada Tsutomu 富山大学, 学術研究部薬学・和漢系, 講師 (00419334)
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Co-Investigator(Kenkyū-buntansha) |
笹岡 利安 富山大学, 学術研究部薬学・和漢系, 教授 (00272906)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | PDGF / VEGF / SDF1 / 血管新生 / 脂肪組織 / 肥満 / エネルギー代謝 |
Outline of Final Research Achievements |
We have reported an important role of PDGF as an angiogenic factor that promotes neovascularization in obese adipose tissue. In the current study, we identified infiltrated adipose tissue macrophages as a major source of PDGF-B which facilitates neovascularization in obese adipose tissue. We have elucidated the molecular mechanisms that glycolytic metabolism and hyperglycemia are key factors for the production of PDGF-B in macrophages. In addition, we have identified SDF1 as a novel player of adipose angiogenesis. SDF1 attenuated angiogenic process of PDGF-B, but the SDF1 protein was degraded by an increase of DPP4 in obese adipose tissue, thereby enhancing the angiogenic effect of PDGF-B as a pathophysiology of obesity development. These findings lead new therapeutic possibilities for improvement of obesity.
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Academic Significance and Societal Importance of the Research Achievements |
内臓脂肪組織の進展は慢性炎症を引き起こし、インスリン抵抗性病態により糖尿病、脂質異常症、高血圧などの様々な疾患の基盤病態を誘導する。脂肪組織の肥大化には、増大した組織を維持する血管新生の進展が不可欠であり、その機序の解明は肥満の抑制による新たな治療法として有用である。本研究では、肥満で脂肪組織に動員されるマクロファージが血管新生因子PDGFを産生することとその分子機構を明らかにした。さらにPDGFによる血管新生を阻害する因子としてSDF1を同定した。肥満の脂肪組織では、SDF1を分解するDPP4の増加によりPDGFによる血管新生が強く誘導され肥満が加速することを、新たな肥満病態として解明した。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Stromal cell-derived factor 1 (SDF1) attenuates platelet-derived growth factor-B (PDGF-B)-induced vascular remodeling for adipose tissue expansion in obesity2020
Author(s)
Watanabe E, Wada T, Okekawa A, Kitamura F, Komatsu G, Onogi Y, Yamamoto S, Sasahara M, Kitada M, Koya D, Tsuneki H, Sasaoka T.
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Journal Title
Angiogenesis .
Volume: 23
Issue: 4
Pages: 667-684
DOI
Related Report
Peer Reviewed / Open Access
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