Inflammatory bowel diseases
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Inflamm. Bowel Dis. · Mar 2015
Endoplasmic reticulum stress and unfolded protein response in inflammatory bowel disease.
In eukaryotic cells, protein folding and modification in the endoplasmic reticulum (ER) is highly sensitive to disturbances of homeostasis. The accumulation of unfolded and misfolded proteins in the ER lumen, termed ER stress, activates intracellular signaling pathways to resolve the protein-folding defect. This unfolded protein response (UPR) increases the capacity of ER protein folding, reduces global protein synthesis, and activates ER-associated protein degradation. ⋯ In addition, a variety of exogenous and endogenous molecules in the intestinal lumen affect ER function, making ER stress and the UPR relevant cellular signals in intestinal homeostasis. Recent studies demonstrated that unresolved ER stress and/or dysregulated UPR may cause inflammatory bowel disease by inducing epithelial cell death, impairing mucosal barrier function, and activating proinflammatory response in the gut. With our increased understanding of ER stress in inflammatory bowel disease pathogenesis, it is now possible to develop novel therapies to improve ER protein-folding homeostasis and target-specific UPR pathways in cells residing in the intestinal mucosa.