Advanced oxidation protein products induce Paneth cells defects by endoplasmic reticulum stress in Crohn's disease

Summary: Paneth cells (PC) play a key role in the innate immune response of intestine epithelium, and PC defects contribute to the pathogenesis of Crohn’s disease (CD). In this study, we utilized active CD tissues and advanced oxidation protein products (AOPP)-challenged C57BL/6 mouse model to inves...

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Main Authors: Jie Shi, Weidong Wang, Shibo Sun, Xiaoping Xu, Jieying Fei, Qian Zhou, Caolitao Qin, Shiyu Ou, Fengfei Wu, Fang ting Wu, Tianyan Xu, Lan Bai, Fang Xie
Format: Article
Language:English
Published: Elsevier 2023-08-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223013895
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author Jie Shi
Weidong Wang
Shibo Sun
Xiaoping Xu
Jieying Fei
Qian Zhou
Caolitao Qin
Shiyu Ou
Fengfei Wu
Fang ting Wu
Tianyan Xu
Lan Bai
Fang Xie
author_facet Jie Shi
Weidong Wang
Shibo Sun
Xiaoping Xu
Jieying Fei
Qian Zhou
Caolitao Qin
Shiyu Ou
Fengfei Wu
Fang ting Wu
Tianyan Xu
Lan Bai
Fang Xie
author_sort Jie Shi
collection DOAJ
description Summary: Paneth cells (PC) play a key role in the innate immune response of intestine epithelium, and PC defects contribute to the pathogenesis of Crohn’s disease (CD). In this study, we utilized active CD tissues and advanced oxidation protein products (AOPP)-challenged C57BL/6 mouse model to investigate the effect of AOPP on PC defects in CD. We found that AOPP accumulated in active CD tissues and was negatively associated with lysozyme expression, while positively correlated with the presence of ER stress markers. Furthermore, AOPP treatment induced PC defects mainly through excessive ER stress in vivo, and AOPP also caused mitochondria-associated ER membranes formation and mitochondrial dysfunction. In addition, the effects of AOPP could be attenuated by the administration of ER stress inhibitor, TUDCA. These findings suggest a pathogenic role of AOPP contributing to PC defects and may provide the basis for developing new strategies to managing CD.
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spelling doaj.art-53524e5020804f5c9a72d84907c5d7312023-07-22T04:52:31ZengElsevieriScience2589-00422023-08-01268107312Advanced oxidation protein products induce Paneth cells defects by endoplasmic reticulum stress in Crohn's diseaseJie Shi0Weidong Wang1Shibo Sun2Xiaoping Xu3Jieying Fei4Qian Zhou5Caolitao Qin6Shiyu Ou7Fengfei Wu8Fang ting Wu9Tianyan Xu10Lan Bai11Fang Xie12Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Gastroenterology, Hunan Provincial People’s Hospital, Changsha, Hunan 410005, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Corresponding authorGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Corresponding authorSummary: Paneth cells (PC) play a key role in the innate immune response of intestine epithelium, and PC defects contribute to the pathogenesis of Crohn’s disease (CD). In this study, we utilized active CD tissues and advanced oxidation protein products (AOPP)-challenged C57BL/6 mouse model to investigate the effect of AOPP on PC defects in CD. We found that AOPP accumulated in active CD tissues and was negatively associated with lysozyme expression, while positively correlated with the presence of ER stress markers. Furthermore, AOPP treatment induced PC defects mainly through excessive ER stress in vivo, and AOPP also caused mitochondria-associated ER membranes formation and mitochondrial dysfunction. In addition, the effects of AOPP could be attenuated by the administration of ER stress inhibitor, TUDCA. These findings suggest a pathogenic role of AOPP contributing to PC defects and may provide the basis for developing new strategies to managing CD.http://www.sciencedirect.com/science/article/pii/S2589004223013895Cell biology
spellingShingle Jie Shi
Weidong Wang
Shibo Sun
Xiaoping Xu
Jieying Fei
Qian Zhou
Caolitao Qin
Shiyu Ou
Fengfei Wu
Fang ting Wu
Tianyan Xu
Lan Bai
Fang Xie
Advanced oxidation protein products induce Paneth cells defects by endoplasmic reticulum stress in Crohn's disease
iScience
Cell biology
title Advanced oxidation protein products induce Paneth cells defects by endoplasmic reticulum stress in Crohn's disease
title_full Advanced oxidation protein products induce Paneth cells defects by endoplasmic reticulum stress in Crohn's disease
title_fullStr Advanced oxidation protein products induce Paneth cells defects by endoplasmic reticulum stress in Crohn's disease
title_full_unstemmed Advanced oxidation protein products induce Paneth cells defects by endoplasmic reticulum stress in Crohn's disease
title_short Advanced oxidation protein products induce Paneth cells defects by endoplasmic reticulum stress in Crohn's disease
title_sort advanced oxidation protein products induce paneth cells defects by endoplasmic reticulum stress in crohn s disease
topic Cell biology
url http://www.sciencedirect.com/science/article/pii/S2589004223013895
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