Upregulation of miR-665 promotes apoptosis and colitis in inflammatory bowel disease by repressing the endoplasmic reticulum stress components XBP1 and ORMDL3.
Moreover, it is now recognized that intestinal inflammation in inflammatory bowel disease (IBD) may arise primarily from IEC dysfunction due to unresolved endoplasmic reticulum (ER) stress as a consequence of genetic disruption of X box binding protein-1 function.
An inability to manage ER stress may not only be a primary originator of intestinal inflammation as exemplified by genetic polymorphisms in XBP1 that are associated with IBD but also a perpetuator of inflammation when ER stress is induced secondarily to inflammatory mediators or microbial factors.
(2008) link a key mediator of endoplasmic reticulum stress, the protein XBP1, with survival of intestinal secretory epithelial cells and inflammatory bowel disease.
An association of XBP1 variants with both forms of human IBD (Crohn's disease and ulcerative colitis) was identified and replicated (rs35873774; p value 1.6 x 10(-5)) with novel, private hypomorphic variants identified as susceptibility factors.