Crosstalk between stress and cytokine signaling in metabolic syndrome

代谢综合征中压力与细胞因子信号传导之间的串扰

• 批准号: 21590067
• 负责人: HAYASHI Hidetoshi
• 金额: $ 2.91万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-21590067/
• 关键词: ストレス; TRB3; TGFβ; 脂肪細胞; β細胞; メタボリックシンドローム; TRB1; 小胞体ストレス; PPARγ; IL-2; perilipin; 脂肪組胞; 脂肪滴; Smad3; 肝細胞; Cdc25A; 膵β細胞; C; EBPβ; RORα

In this study, we examined the crosstalk between stress and inflammatory cytokine signaling in metabolic syndrome using adipocytes, hepatocytes and pancreatic beta cells, especially focused on contribution of the members of pseudokinase family TRBs, which are induced by various stresses.Both signals were strongly attenuated the maturation and function of adipocytes(3T3-L1 cells and HW11 cells). On the other hand, in human hepatoma cell line, HepG2 cells, stress induced TRB3 potently inhibited the signaling of one of the inflammatory cytokines, TGFβ. Moreover the impairment ofβcell line, Min6 cells, induced by endoplasmic reticulum stress is rescued by TGFβ. Our findings suggest that the crosstalk of both signal showed the cell-specific phenotype, and that TRBs proteins function as the tuner of these responses.

在这项研究中，我们使用脂肪细胞、肝细胞和胰岛β细胞来研究应激和炎性细胞因子信号在代谢综合征中的串扰，特别是在不同的应激诱导下，伪激酶家族成员TRBs的作用。这两种信号都强烈地减弱了脂肪细胞(3T3-L1细胞和HW11细胞)的成熟和功能。另一方面，在人肝癌细胞系中，应激诱导的TRB3有效地抑制了炎症细胞因子转化生长因子β的信号转导。此外，内质网应激对β细胞株Min6细胞的损伤也可被转化生长因子β所挽救。我们的发现表明，这两个信号的串扰显示了细胞特有的表型，并且TRBs蛋白作为这些反应的调谐器发挥作用。

项目成果

Two Mechanistically and Temporally Distinct NF-κB Activation Pathways in IL-1 Signaling

• DOI: 10.1126/scisignal.2000387
• 发表时间: 2009-10-20
• 期刊: SCIENCE SIGNALING
• 影响因子: 7.3
• 作者: Yamazaki, Kohsuke;Gohda, Jin;Inoue, Jun-Ichiro
• 通讯作者: Inoue, Jun-Ichiro

Dual mode of regulation of Cdc25A protein by TRB3

TRB3对Cdc25A蛋白的双重调控模式

• 发表时间: 2010
• 期刊: Biol. Pharm. Bull.
• 作者: S. Sakai;N. Ohoka;K. Onozaki;M. Kitagawa;M. Nakanishi;H. Hayashi
• 通讯作者: H. Hayashi

Role of TRB3 function in SREBP-2-regulated cholesterol homeostasis in human hepatoma cells

TRB3功能在SREBP-2调节的人肝癌细胞胆固醇稳态中的作用

• 发表时间: 2011
• 作者: Nobumichi Ohoka;Hidetoshi Hayashi;Mikihiko Naito
• 通讯作者: Mikihiko Naito

ハンチントン病関連遺伝子HAP1の機能解析

亨廷顿病相关基因HAP1的功能分析

• 发表时间: 2010
• 作者: 藤井拓夫;酒井聡;戸田洋平;伊藤友香;篠田晃;林秀敏
• 通讯作者: 林秀敏

Reduction of transforming growth factor-β type II receptor is caused by the enhanced ubiquitin-dependent degradation in human renal cell carcinoma

• DOI: 10.1002/ijc.25164
• 发表时间: 2010-10-01
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Fukasawa, Hirotaka;Yamamoto, Tatsuo;Hishida, Akira
• 通讯作者: Hishida, Akira