ID 112472
著者
Deuschle, Ulrich Phenex Pharmaceuticals AG
Taira, Shu Fukui Prefectural University
Nishida, Takeshi University of Toyama
Fujimoto, Makoto University of Toyama
Hijikata, Takao Musashino University
キーワード
TSOD mice
HCC
Tumor metabolism
Bile acid
Spontaneous tumorigenesis model
資料タイプ
学術雑誌論文
抄録
Background and aims Tsumura-Suzuki obese diabetic (TSOD) is a good model of metabolic syndrome showing typical lesions found in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and develops spontaneous hepatic tumors with a high frequency. Majority of the developing tumors overexpress glutamine synthetase (GS), which is used as a marker of hepatocellular carcinoma (HCC). The aim of this study is to assess the status of expression of metabolism-related genes and the level of bile acids in the TSOD mice-derived tumors and to determine the association with metabolic dysregulation between human HCC and TSOD mice-derived tumors.
Methods GS-positive hepatic tumors or adjacent normal tissues from 71-week-old male TSOD mice were subjected to immunohistochemical staining (IHC), quantitative RT-PCR (qRT-PCR), quantitation of cholic acid and taurocolic acid.
Results We found that downregulation of the rate-limiting enzyme for betaine synthesis (BADH), at both mRNA and protein levels in GS-positive TSOD mice-derived tumors. Furthermore, the bile acid receptor FXR and the bile acid excretion pump BSEP (Abcb11) were found to be downregulated, whereas BAAT and Akr1c14, involved in primary bile acid synthesis and bile acid conjugation, were found to be upregulated at mRNA level in GS-positive TSOD mice-derived tumors. BAAT and Akr1c14 was also overexpressed at protein levels. Total cholic acid was found to be increased in GS-positive TSOD mice-derived tumors.
Conclusion Our results strongly support the significance of TSOD mice as a model of spontaneously developing HCC.
掲載誌名
Hepatology International
ISSN
19360533
19360541
cat書誌ID
AA12728536
出版者
Springer
12
3
開始ページ
254
終了ページ
261
発行日
2018-04-12
権利情報
This is a post-peer-review, pre-copyedit version of an article published in Hepatology International. The final authenticated version is available online at: https://doi.org/10.1007/s12072-018-9860-3
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
著者版
部局
医学系