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However, the precise mechanism of hepatotoxicity and hepatocarcinogenesis caused by excessive cholesterol consumption remains unclear. We aimed to investigate the impact of dietary cholesterol using hepatitis C virus core gene transgenic (HCVcpTg) mice, which spontaneously developed HCC with age. Male HCVcpTg mice were treated for 15months with either a control diet or an isocaloric diet containing 1.5% cholesterol, and liver phenotypes and tumor-associated signaling pathways were evaluated. The high-cholesterol diet-fed HCVcpTg mice exhibited a significantly higher incidence of liver tumors compared with the control diet mice (100% vs. 41%, P\u003c0.001). The diet induced steatohepatitis with pericellular fibrosis and evoked higher mRNA expression of pro-inflammatory and pro-fibrotic mediators along with enhanced hepatocyte proliferation and greater oxidative and endoplasmic reticulum stress in the liver. Moreover, long-term consumption of cholesterol-rich diet activated nuclear factor-kappa B (NF-kappa B) and p62/sequestosome 1 (Sqstm1)-nuclear factor erythroid 2 (NRF2) axis, enhanced fibrogenesis, and consequently accelerated hepatic tumorigenesis. In conclusion, these results demonstrate that a high-cholesterol diet facilitates liver tumorigenesis by inducing steatohepatitis, promoting hepatocyte division, and up-regulating cellular stress and pro-inflammatory NF-kappa B and detoxifying p62/Sqstm1-NRF2 signals. 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A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice (高コレステロール食はHCVコア遺伝子トランスジェニックマウスにおける脂肪性肝炎と肝腫瘍の発生を促進させる)
http://hdl.handle.net/10091/00022152
f3f8a229-c8e0-4409-b749-f521e6a5aaa3
名前 / ファイル | ライセンス | アクション | |
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2020-06-15 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice (高コレステロール食はHCVコア遺伝子トランスジェニックマウスにおける脂肪性肝炎と肝腫瘍の発生を促進させる) | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||
タイプ | doctoral thesis | |||||
著者 |
王, 暁経
× 王, 暁経 |
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出版者 | ||||||
出版者 | 信州大学 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 王 暁経. A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice (高コレステロール食はHCVコア遺伝子トランスジェニックマウスにおける脂肪性肝炎と肝腫瘍の発生を促進させる). 信州大学, 2020, 博士論文. | |||||
書誌情報 |
発行日 2020-03-31 |
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学位授与番号 | ||||||
学位授与番号 | 13601甲第1185号 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2020-03-31 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関名 | ||||||
学位授与機関名 | 信州大学(Shinshu university) | |||||
学位の区分 | ||||||
Doctoral | ||||||
学位の分野 | ||||||
医学 | ||||||
学位の報告番号 | ||||||
甲第1185号 | ||||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 雑誌に発表。ARCHIVES OF TOXICOLOGY. 93(6):1713-1725 (2019); doi:10.1007/s00204-019-02440-7. | |||||
資源タイプ(コンテンツの種類) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Thesis | |||||
PubMed | ||||||
関連識別子 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed&term=31004178 | |||||
関連名称 | ||||||
関連名称 | 31004178 | |||||
DOI | ||||||
関連識別子 | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1007/s00204-019-02440-7 | |||||
関連名称 | ||||||
関連名称 | 10.1007/s00204-019-02440-7 | |||||
権利 | ||||||
権利情報 | This is a post-peer-review, pre-copyedit version of an article published in Archives of Toxicology. The final authenticated version is available online at: https://doi.org/10.1007/s00204-019-02440-7 . | |||||
出版タイプ | ||||||
出版タイプ | NA | |||||
出版タイプResource | http://purl.org/coar/version/c_be7fb7dd8ff6fe43 | |||||
WoS | ||||||
Web of Science | ||||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000475702100018 |