Advanced oxidation protein products induce Paneth cells defects by endoplasmic reticulum stress in Crohn's disease
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
Affiliations
Jie Shi
Guangdong 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, China
Weidong Wang
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
Shibo Sun
Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
Xiaoping Xu
Department of Gastroenterology, Hunan Provincial People’s Hospital, Changsha, Hunan 410005, China
Jieying Fei
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
Qian Zhou
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
Caolitao Qin
Guangdong 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, China
Shiyu Ou
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
Fengfei Wu
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
Fang ting Wu
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
Tianyan Xu
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
Lan Bai
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Corresponding author
Fang Xie
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Corresponding author
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.
