ERdj5 protects goblet cells from endoplasmic reticulum stress-mediated apoptosis under inflammatory conditions

초록

Inflammatory bowel disease: A protective enzyme in intestinal goblet cellsStudies of inflammatory bowel disease (IBD) in mice reveal the role of an enzyme that assists the degradation of mis-folded proteins in the 'goblet' cells involved in producing the mucus barrier that lines and protects the interior of the gut. The most common forms of IBD are ulcerative colitis and Crohn's disease. Researchers in South Korea led by Hyun-Jeong Ko at Kangwon National University, Chuncheon, and Sun-Young Chang at Ajou University, Suwon, compared goblet cell biology in normal mice with mice in which the gene encoding the protein-degrading enzyme ERdj5 had been disabled. This showed that ERdj5 protects goblet cells from a form of stress-mediated cell death that occurs during gut inflammation. The results suggest that drugs modifying the molecular mechanisms underlying ERdj5's actions could open new avenues towards preventing and treating IBD. Endoplasmic reticulum stress is closely associated with the onset and progression of inflammatory bowel disease. ERdj5 is an endoplasmic reticulum-resident protein disulfide reductase that mediates the cleavage and degradation of misfolded proteins. Although ERdj5 expression is significantly higher in the colonic tissues of patients with inflammatory bowel disease than in healthy controls, its role in inflammatory bowel disease has not yet been reported. In the current study, we used ERdj5-knockout mice to investigate the potential roles of ERdj5 in inflammatory bowel disease. ERdj5 deficiency causes severe inflammation in mouse colitis models and weakens gut barrier function by increasing NF-kappa B-mediated inflammation. ERdj5 may not be indispensable for goblet cell function under steady-state conditions, but its deficiency induces goblet cell apoptosis under inflammatory conditions. Treatment of ERdj5-knockout mice with the chemical chaperone ursodeoxycholic acid ameliorated severe colitis by reducing endoplasmic reticulum stress. These findings highlight the important role of ERdj5 in preserving goblet cell viability and function by resolving endoplasmic reticulum stress.

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