The ROS-generating oxidase Nox1 is required for epithelial restitution following colitis.
The ROS-generating oxidase Nox1 is required for epithelial restitution following colitis.
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DOI：
10.1538/expanim.15-0127
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发表时间：
2016-07-29
影响因子：
2.4
通讯作者：
Kamata T
中科院分区：
文献类型：
--
作者：
Kato M;Marumo M;Nakayama J;Matsumoto M;Yabe-Nishimura C;Kamata T
越来越多的证据表明，由内源性代谢酶产生的活性氧（ROS）参与了多种细胞内机制。特别是，产生超氧化物的NADPH氧化酶（Nox）1在结肠中高度表达，并与结肠组织的生理和病理生理状态有关。然而，其在结肠炎后组织修复中的作用尚未完全阐明。我们使用小鼠实验性结肠炎的研究表明，在葡聚糖硫酸钠诱导的结肠炎后，Nox 1缺陷小鼠中没有发生粘膜层的修复。这是伴随着抑制的增殖，细胞存活，迁移，并最终分化（杯状细胞的产生）的隐窝祖细胞，如组织化学分析所确定的。此外，在修复过程中，结肠隐窝中的Nox 1表达以及ROS产生增加，而Nox 1缺陷抑制了这些事件。结果表明，Nox 1通过维持隐窝祖细胞的生物活性来促进结肠粘膜创伤修复，并且在结肠炎相关损伤的情况下在上皮恢复中起关键作用。
Accumulating evidence suggests that reactive oxygen species (ROS) generated by endogenous metabolic enzymes are involved in a variety of intracellular mechanisms. In particular, superoxide-generating NADPH oxidase (Nox) 1 is highly expressed in the colon and has been implicated in physiological and pathophysiological states of colon tissues. However, its role in tissue repair following colitis has not been fully elucidated. Our study using experimental colitis in mice showed that repair of the mucosal layer did not occur in Nox1-deficient mice following dextran sulfate sodium-induced colitis. This was accompanied by inhibition of proliferation, cell survival, migration, and terminal differentiation (generation of goblet cells) of crypt progenitor cells, as determined by histochemical analyses. Furthermore, Nox1 expression as well as ROS production in the colon crypt was increased during the repair process, and Nox1 deficiency suppressed these events. The results suggest that Nox1 promotes colon mucosal wound repair by sustaining the bioactivity of crypt progenitor cells and plays a crucial role in the epithelial restitution in the case of damage associated with colitis.