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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Life Science / Faculty of Advanced Life Science >
Peer-reviewed Journal Articles, etc >
Paneth cell alpha-defensin misfolding correlates with dysbiosis and ileitis in Crohn's disease model mice
| Title: | Paneth cell alpha-defensin misfolding correlates with dysbiosis and ileitis in Crohn's disease model mice |
| Authors: | Shimizu, Yu Browse this author | | Nakamura, Kiminori Browse this author | | Yoshii, Aki Browse this author | | Yokoi, Yuki Browse this author | | Kikuchi, Mani Browse this author | | Shinozaki, Ryuga Browse this author | | Nakamura, Shunta Browse this author | | Ohira, Shuya Browse this author | | Sugimoto, Rina Browse this author | | Ayabe, Tokiyoshi Browse this author →KAKEN DB |
| Issue Date: | Jun-2020 |
| Publisher: | Life Science Alliance |
| Journal Title: | Life Science Alliance |
| Volume: | 3 |
| Issue: | 6 |
| Start Page: | e201900592 |
| Publisher DOI: | 10.26508/lsa.201900592 |
| Abstract: | Crohn's disease (CD) is an intractable inflammatory bowel disease, and dysbiosis, disruption of the intestinal microbiota, is associated with CD pathophysiology. ER stress, disruption of ER homeostasis in Paneth cells of the small intestine, and alpha-defensin misfolding have been reported in CD patients. Because alpha-defensins regulate the composition of the intestinal microbiota, their misfolding may cause dysbiosis. However, whether ER stress, alpha-defensin misfolding, and dysbiosis contribute to the pathophysiology of CD remains unknown. Here, we show that abnormal Paneth cells with markers of ER stress appear in SAMP1/YitFc, a mouse model of CD, along with disease progression. Those mice secrete reduced-form alpha-defensins that lack disulfide bonds into the intestinal lumen, a condition not found in normal mice, and reduced-form alpha-defensins correlate with dysbiosis during disease progression. Moreover, administration of reduced-form alpha-defensins to wild-type mice induces the dysbiosis. These data provide novel insights into CD pathogenesis induced by dysbiosis resulting from Paneth cell alpha-defensin misfolding and they suggest further that Paneth cells may be potential therapeutic targets. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/79209 |
| Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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