...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Hypertonic Stress Increases Claudin-4 Expression And Tight Junction Integrity In Association With Mupp1 In Imcd3 Cells
【24h】

Hypertonic Stress Increases Claudin-4 Expression And Tight Junction Integrity In Association With Mupp1 In Imcd3 Cells

机译：高渗应激会增加Imcd3细胞中与Mupp1相关的Claudin-4表达和紧密连接完整性

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

We reported that the multiple PDZ protein 1 (MUPP1) is an osmotic response protein in kidney cells. This up-regulation was found to be necessary for the maintenance of tight epithelial properties in these cells. We investigated whether an interaction with one or more members of the claudin family is responsible for this observation. In response to hypertonicity, the up-regulation of claudin-4 (Cldn4) expression, and not other claudins, was initially identified in inner medullary collecting duct (IMCD3) cells by gene array and further verified by quantitative PCR and Western blotting. In kidney tissues, Cldn4 expression was substantial in the papilla and absent in the cortex. Furthermore, Cldn4 expression significantly increased in the papilla of mice after 36 h of thirsting. Cldn4 immunofluorescence in hypertonically stressed cells revealed colocalization with MUPP1 at the tight junctions. Interaction between Cldn4 and MUPP1 was also demonstrated by coimmunoprecipitation of both proteins from IMCD3 cells chronically adapted to hypertonicity. In IMCD3 cells stably silenced for MUPP1 expression under hypertonic conditions, a significant decrement in Cldn4 expression was observed that was restored after inhibition of lysosome activity. Immunofluorescence detection identified that in these MUPP1-silenced cells Cldn4 was mistargeted to the lysosomes. Functionally, silencing Cldn4 expression in IMCD3 cells resulted in a decrease in the transepithelial resistance to the same degree as observed when MUPP1 expression was silenced, suggesting that MUPP1 contributes to the maintenance of a tight epithelium in the medulla of the kidney under hypertonic stress by correctly localizing Cldn4 to the tight junctions.
机译：我们报道了多个PDZ蛋白1（MUPP1）是肾细胞中的一种渗透反应蛋白。发现这种上调对于维持这些细胞中紧密的上皮特性是必需的。我们调查了与claudin家族的一个或多个成员的互动是否对此观察负责。响应高渗性，最初通过基因阵列在内髓收集管（IMCD3）细胞中鉴定了claudin-4（Cldn4）表达而非其他claudins的表达上调，并通过定量PCR和Western印迹进一步证实。在肾脏组织中，Cldn4在乳头中大量表达，而在皮质中不存在。此外，口渴36小时后，小鼠乳头中的Cldn4表达显着增加。高渗应激细胞中的Cldn4免疫荧光显示与MUPP1在紧密连接处共定位。 Cldn4和MUPP1之间的相互作用还通过共免疫沉淀来自慢性适应高渗的IMCD3细胞的两种蛋白质而得到证实。在高渗条件下稳定沉默MUPP1表达的IMCD3细胞中，观察到Cldn4表达的显着下降，在抑制溶酶体活性后恢复。免疫荧光检测发现，在这些MUPP1沉默的细胞中，Cldn4被错误地靶向了溶酶体。在功能上，IMCD3细胞中Cldn4表达的沉默导致跨上皮抵抗力的降低与MUPP1表达沉默时所观察到的程度相同，这表明MUPP1有助于通过正确地维持高渗应激下肾脏的髓质中紧密的上皮将Cldn4定位在紧密连接处。

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