フルテキストファイル
著者
Nagahara Ran Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine
Matono Tomomitsu Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine 鳥取大学研究者総覧 KAKEN研究者をさがす
Sugihara Takaaki Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine 鳥取大学研究者総覧 KAKEN研究者をさがす
Matsuki Yukako Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine
Yamane Masafumi Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine
Okamoto Toshiaki Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine
Miyoshi Kenichi Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine 鳥取大学研究者総覧
Nagahara Takakazu Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine
Okano Jun-ichi Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine
Koda Masahiko Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine
Isomoto Hajime Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine 鳥取大学研究者総覧 KAKEN研究者をさがす
キーワード
endoplasmic reticulum stress
mouse model
nonalcoholic fatty liver disease
nonalcoholic steatohepatitis
抄録
Background Nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is a chronic liver disease related to metabolic syndrome that can progress to liver cirrhosis. The involvement of the endoplasmic reticulum (ER) stress response in NAFLD progression and the roles played by activating factor 3 (ATF3) and the downstream nuclear protein 1 (NUPR1) are poorly understood. The aim of this study was to determine the gene expression profiles around the ATF3/NUPR1 axis in relation to the development of NAFLD using novel mouse models.

Methods Fatty liver Shionogi (FLS) mice (n = 12) as a NAFLD model and FLS-ob/ob mice (n = 28) as a NASH model were fed a standard diet. The FLS mice were sacrificed at 24 weeks of age as a control, whereas the FLS-ob/ob mice were sacrificed at 24, 36, and 48 weeks of age. Hepatic steatosis, inflammation, and fibrosis were evaluated by biochemical, histological, and gene expression analyses. The expression levels of the ER-stress related genes Jun proto-oncogene (C-jun), Atf3, Nupr1, and C/EBP homologous protein (Chop) were measured in liver tissue. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.

Results Control mice demonstrated hepatic steatosis alone without apparent fibrosis. On the other hand, FLS-ob/ob mice showed severe steatohepatitis at both 24 and 36 weeks of age and severe fibrosis at both 36 and 48 weeks of age. The expression levels of Atf3, Nupr-1, and C-jun significantly increased from 24 to 48 weeks of age in FLS-ob/ob mice compared with control mice. The expression level of Chop was already high in FLS mice and maintained similar levels in FLS-ob/ob mice; the expression level was consistent with the percentage of TUNEL-positive cells.

Conclusion The ATF3/NUPR1 axis plays a pivotal role in NASH progression in association with C-jun and Chop and appears to induce apoptosis from early steatosis in the NASH model mice.
出版者
Tottori University Medical Press
資料タイプ
学術雑誌論文
外部リンク
ISSN・ISBN
05135710
書誌ID
AA00892882
掲載誌名
Yonago Acta Medica
最新掲載誌名
Yonago Acta Medica
62
1
開始ページ
36
終了ページ
46
発行日
2019-03-28
出版者DOI
著者版フラグ
出版社版
著作権表記
注があるものを除き、この著作物は日本国著作権法により保護されています。 / This work is protected under Japanese Copyright Law unless otherwise noted.
掲載情報
Yonago Acta Medica. 2019, 62(1), 36-46
部局名
医学部・医学系研究科・医学部附属病院
言語
英語