TAK1 binding protein 2 is essential for liver protection from stressors.
TAK1 binding protein 2 is essential for liver protection from stressors.
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DOI：
10.1371/journal.pone.0088037
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ninomiya-Tsuji J
中科院分区：
文献类型：
--
作者：
Ikeda Y;Morioka S;Matsumoto K;Ninomiya-Tsuji J
肝脏是抵御环境压力的第一道防线，肝细胞对环境压力作出反应并进行代谢。因此，肝细胞可被应激源损伤。防止肝细胞损伤和细胞死亡对肝功能和体内平衡很重要。TAK1 （MAP3K7）是几种细胞类型中应激源（如细菌分子诱导的信号转导途径）的中介。Tak1缺乏已被报道可诱发自发性肝细胞癌。然而，TAK1活性在肝脏应激反应中的调节机制尚未明确。在这里，我们报道通过TAK1结合蛋白2 （TAB2）激活TAK1是肝脏免受应激源保护所必需的。我们发现，细菌片段脂多糖（LPS）激活了原代肝细胞中的TAK1，而TAB2的缺失使TAK1活性降低。肝细胞特异性缺失Tab2基因的小鼠仅表现出迟发性中度肝脏病变，但对lps诱导的肝损伤敏感。此外，我们发现化学应激源在肝细胞特异性tab2缺陷小鼠中诱导了严重的肝损伤。这些结果表明，TAB2是肝脏应激条件的传感器，并通过激活TAK1通路来保护肝脏。
The liver is the first line of defense from environmental stressors in that hepatocytes respond to and metabolize them. Hence, hepatocytes can be damaged by stressors. Protection against hepatic cell damage and cell death is important for liver function and homeostasis. TAK1 (MAP3K7) is an intermediate of stressors such as bacterial moieties–induced signal transduction pathways in several cell types. Tak1 deficiency has been reported to induce spontaneous hepatocellular carcinoma. However, the regulatory mechanism of TAK1 activity in liver stress response has not yet been defined. Here we report that activation of TAK1 through TAK1 binding protein 2 (TAB2) is required for liver protection from stressors. We found that a bacterial moiety, lipopolysaccharides (LPS), activated TAK1 in primary hepatocytes, which was diminished by deletion of TAB2. Mice having hepatocyte-specific deletion of the Tab2 gene exhibited only late-onset moderate liver lesions but were hypersensitive to LPS-induced liver injury. Furthermore, we show that a chemical stressor induced greatly exaggerated liver injury in hepatocyte-specific Tab2-deficient mice. These results demonstrate that TAB2 is a sensor of stress conditions in the liver and functions to protect the liver by activating the TAK1 pathway.
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影响因子：
8
作者：
Morioka, S.;Omori, E.;Kajino, T.;Kajino-Sakamoto, R.;Matsumoto, K.;Ninomiya-Tsuji, J.
通讯作者：
Ninomiya-Tsuji, J.
影响因子：
11.2
作者：
Omori E;Matsumoto K;Zhu S;Smart RC;Ninomiya-Tsuji J
通讯作者：
Ninomiya-Tsuji J
DOI：
10.4049/jimmunol.0903587
发表时间：
2010-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kajino-Sakamoto R;Omori E;Nighot PK;Blikslager AT;Matsumoto K;Ninomiya-Tsuji J
通讯作者：
Ninomiya-Tsuji J
影响因子：
4.8
作者：
Kishimoto, K;Matsumoto, K;Ninomiya-Tsuji, J
通讯作者：
Ninomiya-Tsuji, J
影响因子：
50.3
作者：
He G;Yu GY;Temkin V;Ogata H;Kuntzen C;Sakurai T;Sieghart W;Peck-Radosavljevic M;Leffert HL;Karin M
通讯作者：
Karin M