the effects of CD206-positive macrophages on obesity-associated liver tumors
| Project/Area Number |
16K09777
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Dokkyo Medical University (2017-2018)
University of Toyama (2016) |
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Principal Investigator |
USUI ISAO 獨協医科大学, 医学部, 教授 (50377272)
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| Co-Investigator(Kenkyū-buntansha) |
早川 芳弘 富山大学, 和漢医薬学総合研究所, 教授 (10541956)
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| Research Collaborator |
NAKAGAWA takashi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | 肝がん / 肥満 / 糖尿病 / マクロファージ / HIF-1a / マウス / 肥満症 / 1 肝がん / 2 肥満 / 3 マクロファージ |
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| Outline of Final Research Achievements |
The incidence of cancers increases in obese and/or diabetic patients. In this study, we examined the relationship between altered macrophage polarity and development of liver cancer by using DEN, a chemical carcinogen, -induced mouse liver cancer model. High fat diet-induced obesity increased the number of liver cancer. Ablation of CD206-positive macrophages by about 40 % did not affect the incidence of liver cancer. On the other hand, macrophage-specific HIF-1alpha deletion decreased the number of liver cancer by about 50 %, which was associated with decreased activation of inflammatory signaling and ERK in liver.
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| Academic Significance and Societal Importance of the Research Achievements |
肝がんは肥満症や糖尿病に合併しやすいがんの一つである。本研究計画では、腫瘍周囲に浸潤するマクロファージという免疫細胞に注目し検討を行った。肥満糖尿病マウスでは肝がんの発症が促進されるが、マクロファージに発現するHIF-1alphaという転写因子を抑制することで、肝がんの発症を抑制しうることを示した。従来CD206をマーカーとするマクロファージががんの増殖に促進的な役割を担うことが知られていた。しかし、単にその数を減らすのではなく、HIF-1alphaを抑制することによりがんの抑制が期待できるという新しい予防・治療の概念を提唱したところに本研究の意義がある。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] A subset of cerebrovascular pericytes originates from mature macrophages in the very early phase of vascular development in CNS.2017
Author(s)
S. Yamamoto, M. Muramatsu, E. Azuma, M. Ikutani, Y. Nagai, H. Sagara, B.N. Koo, S. Kita, E. O’Donnell, T. Osawa, H. Takahashi, K.I. Takano, M. Dohmoto, M. Sugimori, I. Usui, Y. Watanabe, N. Hatakeyama, T. Iwamoto, I. Komuro, K. Takatsu, K. Tobe, S. Niida, N. Matsuda, M. Shibuya, M. Sasahara
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Journal Title
Sci Rep
Volume: 7：3855
Issue: 1
Pages: 1-16
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] HIF-1α in Myeloid Cells Promotes Adipose Tissue Remodeling Toward Insulin Resistance.2016
Author(s)
Takikawa A, Mahmood A, Nawaz A, Kado T, Okabe K, Yamamoto S, Arif A, Senda S, Tsuneyama K, Ikutani M, Watanabe Y, Igarashi Y, Nagai Y, Takatsu K, Koizumi K, Imura J, Goda N, Sasahara M, Matsumoto M, Saeki K, Nakagawa T, Fujisaka S, Usui I, Tobe K.
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Journal Title
Diabetes
Volume: 65(12)
Issue: 12
Pages: 3649-3659
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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