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Hepatic expression of the SPTLC3 subunit of serine palmitoyltransferase is associated with development of hepatocellular carcinoma in a mouse model of nonalcoholic steatohepatitis
http://hdl.handle.net/10232/25081
http://hdl.handle.net/10232/25081d921e22e-7034-46ab-8e45-97f18fd2b7ca
Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2016-01-26 | |||||
タイトル | ||||||
タイトル | Hepatic expression of the SPTLC3 subunit of serine palmitoyltransferase is associated with development of hepatocellular carcinoma in a mouse model of nonalcoholic steatohepatitis | |||||
言語 | en | |||||
著者 |
吉嶺, 陽造
× 吉嶺, 陽造 |
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言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
資源タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
要約(Abstract) | ||||||
内容記述タイプ | Other | |||||
内容記述 | The molecular mechanisms underlying the progression of nonalcoholic steatohepatitis (NASH) have not been fully elucidated. The aim of this study was to identify factors involved in NASH progression by analysis of pathophysiological features and gene-expression profiles in livers of STAM mice, a model of NASH-associated hepatocarcinogenesis. C57BL/6N (B6N) mice were injected with streptozotocin to generate STAM mice. Four-week-old male STAM and B6N mice were fed a high-fat diet (HFD) (STAM-F, B6N-F) or a conventional diet (STAM-C, B6N-C) until they were 10, 14, or 18 weeks old. Blood glucose and nonalcoholic fatty liver disease (NAFLD) activity scores of STAM-F were higher than those of STAM-C during all observation periods. STAM-F mice had more severe hepatic fibrosis at 14 weeks, and exhibited higher levels of α-fetoprotein-positive hepatic tumor formation with multiplication than STAM-C mice at 18 weeks. At 14 weeks, cDNA microarray analysis revealed that the hepatic expression of eight mRNAs was ≥30-fold higher in STAM-F than B6N-F mice. The expression of another four genes was increased ≥5-fold in STAM-F than B6N-F mice, and ≥5-fold in B6N-F relative to B6N-C mice. Of the 12 genes, the difference in Sptlc3 mRNA expression was most pronounced, and gradually increased over time, as determined by quantitative RT-PCR in STAM-F mice. In addition, Sptlc3 mRNA expression in STAM-F mice was higher than that in db/db micethat received HFD and in B6N mice fed a choline‑deficient L-amino acid (CDAA)-defined diet. In conclusion, a high-fat diet aggravated pathophysiological findings in the liver in NASH mouse models, and the hepatic expression of Sptlc3 mRNA was potentially associated with NASH progression. Yozo Yoshimine, Hirofumi Uto, Kotaro Kumagai, Seiichi Mawatari, Shiho Arima, Rie Ibusuki, Kumiko Mera, Tsuyoshi Nosaki, Shuji Kanmura, Masatsugu Numata, Tsutomu Tamai, Akihiro Moriuchi, Hirohito Tsubouchi and Akio Ido Hepatic expression of the Sptlc3 subunit of serine palmitoyltransferase is associated with the development of hepatocellular carcinoma in a mouse model of nonalcoholic steatohepatitis ONCOLOGY REPORTS 33: 1657-1666, 2015 doi: https://doi.org/10.3892/or.2015.3745 |
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言語 | en | |||||
収録雑誌名 |
en : ONCOLOGY REPORTS 巻 33, p. 1657-1666, 発行日 2015 |
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作成日 | ||||||
日付 | 2015-07-17 | |||||
日付タイプ | Collected | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.3892/or.2015.3745 | |||||
出版タイプ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
NDC | ||||||
主題Scheme | NDC | |||||
主題 | 490 | |||||
ファイル(説明) | ||||||
内容記述タイプ | Other | |||||
内容記述 | 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨 | |||||
言語 | ja | |||||
公開者・出版者 | ||||||
出版者 | ONCOLOGY | |||||
言語 | en | |||||
公開者・出版者 | ||||||
出版者 | 鹿児島大学 | |||||
言語 | ja | |||||
備考 | ||||||
言語 | ja | |||||
値 | 【指導教員: 井戸章雄】 | |||||
date.appl | ||||||
値 | 【学位申請日】2015-02-04 | |||||
学位名 | ||||||
言語 | ja | |||||
学位名 | 博士(医学) | |||||
学位名 | ||||||
言語 | en | |||||
学位名 | Doctor of Philosophy in Medical Science | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 17701 | |||||
言語 | ja | |||||
学位授与機関名 | 鹿児島大学 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2015-06-30 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲総研第333号 |