Crosstalk between iron metabolic disorder and lipid metabolic disorder in hepatocarcinogenesis

铁代谢紊乱与脂质代谢紊乱在肝癌发生中的串扰

• 批准号: 20590782
• 负责人: HINO Keisuke
• 金额: $ 3万
• 依托单位: Kawasaki Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590782/
• 关键词: C型肝炎ウイルス; 肝発癌; 鉄代謝; 肝脂肪化; ミトコンドリア; 小胞体ストレス; C型肝炎; 鉄; 活性酸素; グリチルリチン; トランスジェニックマウス; 鉄過剰; SREBP1

Metabolic disorders such as iron overload and/or fatty deposition in the liver are one of the well-known pathophysiological features in hepatitis C virus (HCV)-associated hepatocarcinogenesis. Using male transgenic mice expressing the HCV polyprotein which develop hepatic steatosis followed by hepatocellular carcinoma in the presence of hepatic iron overload, we investigated the mechanisms by which hepatic iron overload contributed to the development of hepatic steatosis. Hepatic iron levels were positively correlated with triglyceride concentrations in the liver. Iron-related oxidative stress aggravated mitochondrial injury leading to reduced expression of carnitine palmitoyl transferase I, and induced unfolded protein response which in turn increased the expression of sterol-regulatory element binding protein I, a transcription factor involved in lipid synthesis.

代谢紊乱，如铁超载和/或脂肪沉积在肝脏中是众所周知的病理生理特征之一，在丙型肝炎病毒（HCV）相关的肝癌。使用表达HCV多聚蛋白的雄性转基因小鼠，其在肝铁过载的存在下发生肝脂肪变性，随后发生肝细胞癌，我们研究了肝铁过载导致肝脂肪变性发展的机制。肝脏铁水平与肝脏甘油三酯浓度呈正相关。铁相关的氧化应激加重线粒体损伤，导致肉毒碱棕榈酰转移酶I的表达减少，并诱导未折叠的蛋白质反应，这反过来又增加了固醇调节元件结合蛋白I，参与脂质合成的转录因子的表达。

项目成果

Recommendation of Lamivudine-to-Entecavir switching treatment in chronic hepatitis B responders : Randomized controlled trial

慢性乙型肝炎反应者拉米夫定改为恩替卡韦转换治疗的建议：随机对照试验

• 发表时间: 2011
• 期刊: Hepatol Res
• 影响因子: 4.2
• 作者: Onoue M;Nishimura T(7番目);他全12名;Tanaka Y
• 通讯作者: Tanaka Y

Effects of a late evening snack combined with alpha-glucosidase inhibitor on liver cirrhosis.

深夜零食联合α-葡萄糖苷酶抑制剂对肝硬化的影响。

• 发表时间: 2008
• 期刊: Hepatology Research 38(11)
• 作者: Korenaga K;Korenaga M
• 通讯作者: Korenaga M

Iron overload causes hepatic steatosis through the endopasmic reticulum stress in transgenic mice expressing the hepatitis C virus polyprotein.

在表达丙型肝炎病毒多蛋白的转基因小鼠中，铁超载通过内质网应激导致肝脂肪变性。

• 发表时间: 2008
• 作者: Nishina S;Hino K;Korenaga M;et al
• 通讯作者: et al

Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C

IL28B 与聚乙二醇干扰素-α 和利巴韦林治疗慢性丙型肝炎的反应的全基因组关联

• 发表时间: 2009
• 期刊: Nat. Genet. 41
• 作者: Tanaka Y;Nishida N;Sugiyama M;Kurosaki M;Matsuura K;Sakamoto N;Nakagawa M;Korenaga M;Hino K;Hige S;Ito Y;Mita E;Tanaka E;Mochida S;Murawaki Y;Honda M;Sakai A;Hiasa Y;Nishiguchi S;Koike A;Sakaida I;Imamura M;Ito K;Yano K;Masaki N;S
• 通讯作者: S

A glycyrrhizin-containing preparation reduces hepatic steatosis induced by hepatitis C virus protein and iron in mice

• DOI: 10.1111/j.1478-3231.2011.02469.x
• 发表时间: 2011-04-01
• 期刊: LIVER INTERNATIONAL
• 影响因子: 6.7
• 作者: Korenaga, Masaaki;Hidaka, Isao;Hino, Keisuke
• 通讯作者: Hino, Keisuke