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ID 115504
タイトル別表記
Macrophage HIF-1α increases liver tumor
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
キーワード
Hypoxia-inducible factor-1α
Liver cancer
Macrophage
資料タイプ
学術雑誌論文
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
ISSN
20401124
cat書誌ID
AA12488319
出版者
Asian Association for the Study of Diabetes|John Wiley & Sons
10
6
開始ページ
1411
終了ページ
1418
発行日
2019-03-21
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.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系