Macrophage HIF-1α increases liver tumor
Takikawa, Akiko University of Toyama
Usui, Isao University of Toyama|Dokkyo Medical University
Fujisaka, Shiho University of Toyama
Tsuneyama, Koichi Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
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
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.
Journal of Diabetes Investigation
Asian Association for the Study of Diabetes|John Wiley & Sons
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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