@article{oai:shiga-med.repo.nii.ac.jp:00003828,
 author = {西野, 恭平 and 西田, 淳史 and 稲富, 理 and 今井, 隆行 and 久米, 真司 and 河原, 真大 and 前川, 聡 and 安藤, 朗 and NISHINO, Kyohei and NISHIDA, Atsushi and INATOMI, Osamu and IMAI, Takayuki and KUME, Shinji and KAWAHARA, Masahiro and MAEGAWA, Hiroshi and ANDOH, Akira},
 issue = {2},
 journal = {Journal of Clinical Biochemistry and Nutrition},
 month = {},
 note = {pdf, Autophagy-associated genes have been identified as susceptible loci for inflammatory bowel disease. We investigated the role of a core autophagy factor, Atg5, in the development of dextran sodium sulfate (DSS)-induced colitis. Intestinal epithelial cell (IEC)-specific Atg5 gene deficient mice (Atg5ΔIEC mice) were generated by cross of Atg5-floxed mice (Atg5fl/fl) with transgenic mice expressing Cre-recombinase driven by the villin promotor. Mice were given three cycles of 1.5% DSS in drinking water for 5 days and regular water for 14 days over a 60-day period. The dysfunction of autophagy characterized by a marked accumulation of p62 protein, a substrate for autophagy degradation, was detected in epithelial cells in the non-inflamed and inflamed mucosa of inflammatory bowel disease patients. DSS-colitis was exacerbated in Atg5ΔIEC mice compared to control Atg5fl/fl mice. Phosphorylation of inositol-requiring transmembrane kinase/endonuclease1α (IRE1α), a sensor for endoplasmic reticulum stress, and c-Jun N-terminal kinase, a downstream target of IRE1α, were significantly enhanced in IECs in DSS-treated Atg5ΔIEC mice. Accumulation of phosphorylated IRE1α was enhanced by the treatment with chloroquine, an autophagy inhibitor. Apoptotic IECs were more abundant in DSS-treated Atg5ΔIEC mice. These findings suggest that Atg5 suppresses endoplasmic reticulum stress-induced apoptosis of IECs via the degradation of excess p-IRE1α., Journal Article},
 pages = {156--163},
 title = {Targeted deletion of Atg5 in intestinal epithelial cells promotes dextran sodium sulfate-induced colitis.},
 volume = {68},
 year = {2021}
}