ID | 115504 |
タイトル別表記 | Macrophage HIF-1α increases liver tumor
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著者 |
Takikawa, Akiko
University of Toyama
Usui, Isao
University of Toyama|Dokkyo Medical University
Fujisaka, Shiho
University of Toyama
Okabe, Keisuke
University of Toyama
Nakagawa, Takashi
University of Toyama
Nawaz, Allah
University of Toyama
Kado, Tomonobu
University of Toyama
Jojima, Teruo
Dokkyo Medical University
Aso, Yoshimasa
Dokkyo Medical University
Hayakawa, Yoshihiro
University of Toyama
Yagi, Kunikimi
University of Toyama
Tobe, Kazuyuki
University of Toyama
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キーワード | Hypoxia-inducible factor-1α
Liver cancer
Macrophage
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資料タイプ |
学術雑誌論文
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抄録 | Aims/Introduction: Chronic inflammation of the liver is often observed with obesity or type 2 diabetes. In these pathological conditions, the immunological cells, such as macrophages, play important roles in the development or growth of liver cancer. Recently, it was reported that hypoxia‐inducible factor‐1α (HIF‐1α) is a key molecule for the acquisition of inflammatory M1 polarity of macrophages. In the present study, we examined the effects of altered macrophage polarity on obesity‐ and diabetes‐associated liver cancer using macrophage‐specific HIF‐1α knockout (KO) mice.
Materials and Methods: To induce liver cancer in the mice, diethylnitrosamine, a chemical carcinogen, was used. Both KO mice and wild‐type littermates were fed either a high‐fat diet (HFD) or normal chow. They were mainly analyzed 6 months after HFD feeding. Results: Development of liver cancer after HFD feeding was 45% less in KO mice than in wild‐type littermates mice. Phosphorylation of extracellular signal‐regulated kinase 2 was also lower in the liver of KO mice. Those effects of HIF‐1α deletion in macrophages were not observed in normal chow‐fed mice. Furthermore, the size of liver tumors did not differ between KO and wild‐type littermates mice, even those on a HFD. These results suggest that the activation of macrophage HIF‐1α by HFD is involved not in the growth, but in the development of liver cancer with the enhanced oncogenic extracellular signal‐regulated kinase 2 signaling in hepatocytes. Conclusions: The activation of macrophage HIF‐1α might play important roles in the development of liver cancer associated with diet‐induced obesity and diabetes. |
掲載誌名 |
Journal of Diabetes Investigation
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ISSN | 20401124
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cat書誌ID | AA12488319
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出版者 | Asian Association for the Study of Diabetes|John Wiley & Sons
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巻 | 10
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号 | 6
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開始ページ | 1411
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終了ページ | 1418
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発行日 | 2019-03-21
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権利情報 | This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License(https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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言語 |
eng
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著者版フラグ |
出版社版
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部局 |
医学系
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