Zhang Hai-Sheng, Chen Ying, Fan Li, Xi Qiu-Lei, Wu Guo-Hao, Li Xiu-Xiu, Yuan Tang-Long, He Sheng-Qi, Yu Yue, Shao Meng-Le, Liu Yang, Bai Chen-Guang, Ling Zhi-Qiang, Li Min, Liu Yong, Fang Jing
From the Laboratory of Food Safety Research, Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031.
the Department of Surgery, Zhongshan Hospital, Fudan University School of Medicine, Shanghai 200030.
J Biol Chem. 2015 Jun 12;290(24):15327-36. doi: 10.1074/jbc.M114.633560. Epub 2015 Apr 29.
Intestinal epithelial cells (IECs) have critical roles in maintaining homeostasis of intestinal epithelium. Endoplasmic reticulum (ER) stress is implicated in intestinal epithelium homeostasis and inflammatory bowel disease; however, it remains elusive whether IRE1α, a major sensor of ER stress, is directly involved in these processes. We demonstrate here that genetic ablation of Ire1α in IECs leads to spontaneous colitis in mice. Deletion of IRE1α in IECs results in loss of goblet cells and failure of intestinal epithelial barrier function. IRE1α deficiency induces cell apoptosis through induction of CHOP, the pro-apoptotic protein, and sensitizes cells to lipopolysaccharide, an endotoxin from bacteria. IRE1α deficiency confers upon mice higher susceptibility to chemical-induced colitis. These results suggest that IRE1α functions to maintain the intestinal epithelial homeostasis and plays an important role in defending against inflammation bowel diseases.
肠上皮细胞（IECs）在维持肠道上皮的稳态中起着关键作用。内质网（ER）应激与肠道上皮稳态和炎症性肠病有关；然而，内质网应激的主要传感器肌醇需求酶1α（IRE1α）是否直接参与这些过程仍不清楚。我们在此证明，IECs中Ire1α的基因敲除会导致小鼠自发性结肠炎。IECs中IRE1α的缺失导致杯状细胞丢失和肠道上皮屏障功能丧失。IRE1α缺乏通过诱导促凋亡蛋白CHOP诱导细胞凋亡，并使细胞对内毒素脂多糖敏感。IRE1α缺乏使小鼠对化学诱导的结肠炎更易感。这些结果表明，IRE1α在维持肠道上皮稳态中发挥作用，并在抵御炎症性肠病中起重要作用。
