PubMed | CAS Shanghai Institutes for Biological Sciences, Zhejiang Cancer Hospital and Zhejiang Cancer Center, Sun Yat Sen University, Shanghai University and The University of Oklahoma Health Sciences Center
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2015
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 IRE1, a major sensor of ER stress, is directly involved in these processes. We demonstrate here that genetic ablation of Ire1 in IECs leads to spontaneous colitis in mice. Deletion of IRE1 in IECs results in loss of goblet cells and failure of intestinal epithelial barrier function. IRE1 deficiency induces cell apoptosis through induction of CHOP, the pro-apoptotic protein, and sensitizes cells to lipopolysaccharide, an endotoxin from bacteria. IRE1 deficiency confers upon mice higher susceptibility to chemical-induced colitis. These results suggest that IRE1 functions to maintain the intestinal epithelial homeostasis and plays an important role in defending against inflammation bowel diseases.