Female GADD34 mice develop age‐related inflammation and hepatocellular carcinoma

Aim To analyze the impact of sex on GADD34 function, we studied the aging of female GADD34‐deficient mice and compared them with male GADD34‐deficient mice. Methods We used GADD34‐deficient mice on a C57BL/6 background. These mice were fed a normal diet throughout their life. Alternatively, they wer...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Geriatrics & gerontology international 2017-12, Vol.17 (12), p.2593-2601
Hauptverfasser: Nishio, Naomi, Hasegawa, Tadao, Tatsuno, Ichiro, Isaka, Masanori, Isobe, Ken‐ichi
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Aim To analyze the impact of sex on GADD34 function, we studied the aging of female GADD34‐deficient mice and compared them with male GADD34‐deficient mice. Methods We used GADD34‐deficient mice on a C57BL/6 background. These mice were fed a normal diet throughout their life. Alternatively, they were fed a high‐fat diet at 3 months‐of‐age. Liver tissues taken from mice were analyzed by hematoxylin–eosin staining and immunohistochemical methods. Fresh liver cells were analyzed by flow cytometry. Results We found that female GADD34‐deficient mice did not develop obesity or fatty livers. However, female GADD34‐deficient mice had infiltrations of myeloid cells in the liver, followed by liver atrophy. Many female GADD34‐deficient mice developed hepatocellular carcinoma, whereas female wild‐type (WT) mice did not show hepatocellular carcinoma during aging. Female GADD34‐deficient mice and female WT mice developed the same percentages of lymphoma. Although a high‐fat diet induced a higher level of steatosis in young male GADD34‐deficient mice compared with WT mice, a high‐fat diet induced the same level of steatosis in young female GADD34‐deficient mice compared with WT mice. However, GADD34‐deficient female young mice had a higher level of infiltration of myeloid cells and myofibroblasts than WT mice. Conclusions In contrast to male GADD34‐deficient mice, female GADD34‐deficient mice did not show obesity as they aged. However, similar to the males, they developed inflammation followed by hepatocellular carcinoma. Geriatr Gerontol Int 2017; 17: 2593–2601.
ISSN:1444-1586
1447-0594
DOI:10.1111/ggi.13080