TGF-beta-activated kinase 1 signaling maintains intestinal integrity by preventing accumulation of reactive oxygen species in the intestinal epithelium.
TGF-beta-activated kinase 1 signaling maintains intestinal integrity by preventing accumulation of reactive oxygen species in the intestinal epithelium.
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DOI：
10.4049/jimmunol.0903587
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发表时间：
2010-10-15
期刊：
影响因子：
--
通讯作者：
Ninomiya-Tsuji J
中科院分区：
文献类型：
--
作者：
Kajino-Sakamoto R;Omori E;Nighot PK;Blikslager AT;Matsumoto K;Ninomiya-Tsuji J
肠上皮不断暴露于活性氧（ROS）诱导剂，例如共生微生物。 ROS 水平通常维持在无毒水平，但 ROS 失调与肠道炎症性疾病有关。在此，我们报道 TGFβ 激活激酶 1 (TAK1) 是肠上皮细胞中 ROS 的关键调节因子。小鼠肠上皮中的 tak1 基因缺失导致组织损伤，包括肠上皮细胞凋亡、紧密连接破坏和炎症。 TNF 信号传导是主要的肠道损伤诱导剂，其破坏可以挽救炎症状况，但不能挽救 TAK1 缺陷型肠上皮中的细胞凋亡或紧密连接破坏，这表明 TNF 不是 TAK1 缺陷型肠上皮中注意到的损伤的主要诱导剂。我们发现 TAK1 缺陷导致多个抗氧化反应基因的表达减少，并降低关键抗氧化转录因子 NF-E2 相关因子 2 (Nrf2) 的蛋白水平，从而导致 ROS 积累。外源抗氧化剂治疗可以减少 TAK1 缺陷的肠上皮细胞的细胞凋亡和紧密连接的破坏。因此，TAK1 信号通过 Nrf2 调节 ROS，这对于肠上皮完整性很重要。
The intestinal epithelium is constantly exposed to inducers of reactive oxygen species (ROS) such as commensal microorganisms. Levels of ROS are normally maintained at non-toxic levels, but dysregulation of ROS is involved in intestinal inflammatory diseases. Here we report that TGFβ-activated kinase 1 (TAK1) is a key regulator of ROS in the intestinal epithelium. tak1 gene deletion in the mouse intestinal epithelium caused tissue damage involving enterocyte apoptosis, disruption of tight junctions and inflammation. Disruption of TNF signaling, which is a major intestinal damage inducer, rescued the inflammatory conditions but not apoptosis or disruption of tight junctions in the TAK1-deficient intestinal epithelium, suggesting that TNF is not a primary inducer of the damage noted in TAK1-deficient intestinal epithelium. We found that TAK1 deficiency resulted in reduced expression of several antioxidant responsive genes and reduced the protein level of a key antioxidant transcription factor NF-E2-related factor 2 (Nrf2), which resulted in accumulation of ROS. Exogenous antioxidant treatment could reduce apoptosis and disruption of tight junctions in the TAK1-deficient intestinal epithelium. Thus, TAK1 signaling regulates ROS through Nrf2, which is important for intestinal epithelial integrity.
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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：
16
作者：
Kim, You-Sun;Morgan, Michael J.;Liu, Zheng-Gang
通讯作者：
Liu, Zheng-Gang
DOI：
10.1152/ajpgi.00183.2006
发表时间：
2007-02-01
影响因子：
4.5
作者：
Moeser, Adam J.;Nighot, Prashant K.;Blikslager, Anthony T.
通讯作者：
Blikslager, Anthony T.
影响因子：
4.8
作者：
Kim, Jae-Young;Omori, Emily;Ninomiya-Tsuji, Jun
通讯作者：
Ninomiya-Tsuji, Jun
DOI：
10.1073/pnas.0603089103
发表时间：
2006-08-01
影响因子：
11.1
作者：
Liu, Hong-Hsing;Xie, Min;Chen, Zhijian J.
通讯作者：
Chen, Zhijian J.