ERdj5 protects goblet cells from endoplasmic reticulum stress-mediated apoptosis under inflammatory conditions
Hyunjin Jeong, Eun‐Hye Hong, Jae-Hee Ahn, Jaewon Cho, Jae-Hyeon Jeong, Chaewon Kim, Byung–Il Yoon, Ja Hyun Koo, Yun‐Yong Park, Yoon Mee Yang, Takao Iwawaki, Bruce A. Vallance, Sun‐Young Chang, Hyun‐Jeong Ko
Abstract
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-κB-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.