Increased sensitivity to dextran sodium sulfate colitis in IRE1β-deficient mice
Increased sensitivity to dextran sodium sulfate colitis in IRE1β-deficient mice
复制标题
DOI：
10.1172/jci11476
复制
发表时间：
2001-03-01
影响因子：
15.9
通讯作者：
Ron, D
中科院分区：
文献类型：
--
作者：
Bertolotti, A;Wang, XZ;Ron, D
胃肠道上皮细胞暴露在毒素和感染剂中，这些毒素和感染剂可以对内质网(ER)中的蛋白质折叠产生不利影响，并导致ER应激。IRE1基因与内质网应激信号的感应和响应有关。我们发现胃肠道上皮细胞表达IRE-1β，这是IRE-1的一种特殊亚型。ER应激的标志物Bip-prorein在IRE1β(-/-)小鼠的结肠粘膜中升高，当接触葡聚糖硫酸钠(DSS)诱导炎症性肠病时，突变小鼠比野生型或IRE1β(+/-)小鼠提前3-5天发生结肠炎，炎症标志物ICAM-1在DSS处理的IRE1β(-/-)小鼠的结肠粘膜中也较早表达，表明该突变在炎症过程的早期就有影响。在粘膜溃烂开始之前。这些发现与ER功能的扰动参与结肠炎的发展的模型是一致的，ER功能的扰动通常会被IRE1β的活动缓解。
The epithelial cells of the gastrointestinal tract are exposed to toxins and infectious agents that can adversely affect protein folding in the endoplasmic reticulum (ER) and cause ER stress. The IRE1 genes are implicated in sensing and responding to ER stress signals. We found that epithelial cells of the gastrointestinal tract express IRE 1 beta, a specific isoform of IRE 1. BiP pro rein, a marker of ER stress, was elevated in the colonic mucosa of IRE1 beta (-/-) mice, and, when exposed to dextran sodium sulfate (DSS) to induce inflammatory bowel disease, mutant mice developed colitis 3-5 days earlier than did wild-type or IRE1 beta (+/-) mice, The inflammation marker ICAM-1 was also expressed earlier in the colonic mucosa of DSS-treated IRE1 beta (-/-) mice, indicating that the mutation had its impact early in the inflammatory process, before the onset of mucosal ulceration. These findings are consistent with a model whereby perturbations in ER function, which are normally mitigated by the activity of IRE1 beta, participate in the development of colitis.