Bcl-2 network and regulation of cell death in non-alcoholic steatohepatitis

Bcl-2网络与非酒精性脂肪性肝炎细胞死亡的调节

• 批准号: 21659188
• 负责人: TAKEHARA Tetsuo
• 金额: $ 2.11万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21659188/
• 关键词: アポトーシス; Bcl-2; 肝細胞; Bcl-xL; Mcl-1; Bak; NASH; ノックアウトマウス; 肝線維化; 肝癌; Bid; apoptosis; ノックアウト; Cre

Apoptosis is a characteristic feature for hepatocyte cell death in non-alcoholic steatohepatitis. The aim of this study is to examine the significance and regulation of hepatocyte apoptosis, using several kinds of knockout mice targeting the Bcl-2 family genes. The study revealed that hepatocyte apoptosis is regulated by a fine balance between anti-apoptotic and pro-apoptotic Bcl-2 family and that excessive apoptosis is directly linked to hepatocarcinogenesis.

凋亡是非酒精性脂肪性肝炎中肝细胞细胞死亡的特征。这项研究的目的是使用针对Bcl-2家族基因的几种敲除小鼠检查肝细胞凋亡的重要性和调节。研究表明，肝细胞凋亡受抗凋亡和促凋亡的Bcl-2家族之间的良好平衡调节，并且过量凋亡与肝癌发生直接相关。

项目成果

ABT-737, a Bad mimetic Bcl-xL inhibitor, enhances the anti-tumor effect of sorafenib against hepatocellular carcinoma

Bad 模拟 Bcl-xL 抑制剂 ABT-737 增强索拉非尼对肝细胞癌的抗肿瘤作用

• 发表时间: 2010
• 作者: Hayato Hikita;Takahiro Kodama;Satoshi Shimizu;Minoru Shigekawa;Atsushi Hosui;Takuya Miyagi;Hisashi Ishida;Tomohide Tatsumi;Tatsuya Kanto;Naoki Hiramatsu;Norio Hayashi;Tetsuo Takehara;H. Hikita ; T. Takehara ; S. Shimizu ; T. Kodama ; W. Li ; M. Shigekawa ; A. Hosui ; T. Miyagi ; H. Ishida ; T. Tatsumi ; T. Kanto ; N. Hiramatsu ; N. Hayashi
• 通讯作者: H. Hikita ; T. Takehara ; S. Shimizu ; T. Kodama ; W. Li ; M. Shigekawa ; A. Hosui ; T. Miyagi ; H. Ishida ; T. Tatsumi ; T. Kanto ; N. Hiramatsu ; N. Hayashi

The let-7 family of microRNAs negatively regulates Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma.

let-7 家族的 microRNA 负向调节 Bcl-xL 表达并增强索拉非尼诱导的人肝细胞癌细胞凋亡。

• 发表时间: 2010
• 期刊: J Hepatol
• 影响因子: 25.7
• 作者: Shimizu S;Takehara T;et al.
• 通讯作者: et al.

BH3-Only Protein Bid Participates in the Bcl-2 Network in Healthy Liver Cells

• DOI: 10.1002/hep.23207
• 发表时间: 2009-12-01
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Hikita, Hayato;Takehara, Tetsuo;Hayashi, Norio
• 通讯作者: Hayashi, Norio

Lack of invariant natural killer cells elicits liver inflammation and predispores to liver fibrosis in mice fed with high-fat-diet.

在高脂肪饮食喂养的小鼠中，缺乏不变的自然杀伤细胞会引发肝脏炎症并促进肝纤维化。

• 发表时间: 2010
• 期刊: J Gastroenterol
• 影响因子: 6.3
• 作者: Miyagi T;Takehara T;et al.
• 通讯作者: et al.

Requirement of BH3-only activator proteins Bid and Bim for apoptosis by genetic ablation of Bcl-xL is completely different between hepatocytes and platelets

肝细胞和血小板之间通过 Bcl-xL 基因消融进行细胞凋亡所需的仅 BH3 激活蛋白 Bid 和 Bim 是完全不同的

• 发表时间: 2011
• 作者: Takahiro Kodama;Hayato Hikita;Tsukasa Kawaguchi;Minoru Shigekawa;Hinako Tsunematsu;Kumiko Nishio;Takatoshi Nawa;Satoshi Shimizu;Takuya Miyagi;Atsushi Hosui;Tomohide Tatsumi;Hisashi Ishida;Tatsuya Kanto;Naoki Hiramatsu;Tetsuo Takehara
• 通讯作者: Tetsuo Takehara