• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >c-Jun NH 2-terminal kinase-2 mediates osmotic stress-induced tight junction disruption in the intestinal epithelium
【24h】

c-Jun NH 2-terminal kinase-2 mediates osmotic stress-induced tight junction disruption in the intestinal epithelium

机译：c-Jun NH 2末端激酶-2介导渗透压诱导的肠上皮紧密连接破坏

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Gastrointestinal epithelium faces osmotic stress, both at physiological and pathophysiological conditions. JNK activation is an immediate cellular response to osmotic stress. We investigated the effect of osmotic stress on intestinal epithelial barrier function and delineated the role of JNK2 in osmotic stress-induced tight junction (TJ) regulation in Caco-2 cell monolayers and ileum of Jnk -/- and Jnk2 -/- mice. The role of JNK activation in osmotic stress-induced TJ disruption was evaluated using JNK-specific inhibitor and antisense oligonucleotides. Furthermore, the effect of cold restraint stress in vivo on TJ integrity was determined in rats. Osmotic stress disrupted TJs and barrier function in Caco-2 cell monolayers without affecting cell viability. Osmotic stress activated JNK1 and JNK2 and the inhibition of JNK by SP600125 attenuated osmotic stress-induced TJ disruption. TJ disruption and barrier dysfunction by osmotic stress was associated with JNK-dependent remodeling of actin cytoskeleton. Knockdown of JNK2 accelerated TJ assembly and attenuated osmotic stress-induced TJ disruption in Caco-2 cell monolayers. In mouse ileum in vitro, osmotic stress increased paracellular permeability, which was attenuated by SP600125. Osmotic stress disrupted actin cytoskeleton and TJs and increased paracellular permeability in the ileum of wild-type and JNK1 -/- mice, but not in JNK2 -/- mouse ileum. Cold restraint stress activated JNK in rat ileum and caused JNK-dependent remodeling of actin cytoskeleton and redistribution of occludin and zona occluden-1 from the intercellular junctions. These results reveal the role of JNK2 in the mechanism of osmotic stress-induced TJ disruption in the intestinal epithelium.
机译：胃肠道上皮在生理和病理生理条件下都面临渗透压。 JNK激活是细胞对渗透压的直接反应。我们调查了渗透压对肠上皮屏障功能的影响，并描述了JNK2在渗透压诱导的紧密连接（TJ）调控中对Caco-2细胞单层和Jnk-/-和Jnk2-//-小鼠回肠的作用。使用JNK特异性抑制剂和反义寡核苷酸评估了JNK激活在渗透压诱导的TJ破坏中的作用。此外，在大鼠中确定了体内冷约束应激对TJ完整性的影响。渗透胁迫破坏了Taco和Caco-2细胞单层的屏障功能，而不影响细胞活力。渗透胁迫激活了JNK1和JNK2，SP600125对JNK的抑制作用减弱了渗透胁迫引起的TJ破坏。渗透压对TJ的破坏和屏障功能障碍与肌动蛋白细胞骨架的JNK依赖性重塑有关。击倒JNK2加速了TJ装配并减弱了Caco-2细胞单层中的渗透胁迫诱导的TJ破坏。在体外小鼠回肠中，渗透压增加了细胞旁通透性，这被SP600125减弱。渗透应激破坏了野生型和JNK1-/-小鼠回肠中的肌动蛋白细胞骨架和TJs，并增加了细胞旁通透性，但在JNK2-/-小鼠回肠中却没有。冷约束应激激活大鼠回肠中的JNK，并导致肌动蛋白细胞骨架的JNK依赖性重塑以及occludin和zona occluden-1从细胞间连接处的重新分布。这些结果揭示了JNK2在渗透应激诱导的肠上皮TJ破坏的机制中的作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号