TAK1 binding protein 2 is essential for liver protection from stressors.
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 intermedi...
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doaj-7bca9e756e6b41b79209b9dd26acd41b2020-11-25T00:24:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8803710.1371/journal.pone.0088037TAK1 binding protein 2 is essential for liver protection from stressors.Yuka IkedaSho MoriokaKunihiro MatsumotoJun Ninomiya-TsujiThe 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.http://europepmc.org/articles/PMC3912198?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuka Ikeda Sho Morioka Kunihiro Matsumoto Jun Ninomiya-Tsuji |
spellingShingle |
Yuka Ikeda Sho Morioka Kunihiro Matsumoto Jun Ninomiya-Tsuji TAK1 binding protein 2 is essential for liver protection from stressors. PLoS ONE |
author_facet |
Yuka Ikeda Sho Morioka Kunihiro Matsumoto Jun Ninomiya-Tsuji |
author_sort |
Yuka Ikeda |
title |
TAK1 binding protein 2 is essential for liver protection from stressors. |
title_short |
TAK1 binding protein 2 is essential for liver protection from stressors. |
title_full |
TAK1 binding protein 2 is essential for liver protection from stressors. |
title_fullStr |
TAK1 binding protein 2 is essential for liver protection from stressors. |
title_full_unstemmed |
TAK1 binding protein 2 is essential for liver protection from stressors. |
title_sort |
tak1 binding protein 2 is essential for liver protection from stressors. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3912198?pdf=render |
work_keys_str_mv |
AT yukaikeda tak1bindingprotein2isessentialforliverprotectionfromstressors AT shomorioka tak1bindingprotein2isessentialforliverprotectionfromstressors AT kunihiromatsumoto tak1bindingprotein2isessentialforliverprotectionfromstressors AT junninomiyatsuji tak1bindingprotein2isessentialforliverprotectionfromstressors |
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