Shi Jie, Wang Weidong, Sun Shibo, Xu Xiaoping, Fei Jieying, Zhou Qian, Qin Caolitao, Ou Shiyu, Wu Fengfei, Wu Fang Ting, Xu Tianyan, Bai Lan, Xie Fang
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.
iScience. 2023 Jul 10;26(8):107312. doi: 10.1016/j.isci.2023.107312. eCollection 2023 Aug 18.
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 , 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.
潘氏细胞（PC）在肠道上皮的固有免疫反应中起关键作用，且潘氏细胞缺陷会导致克罗恩病（CD）的发病机制。在本研究中，我们利用活动期CD组织和经高级氧化蛋白产物（AOPP）刺激的C57BL/6小鼠模型，来研究AOPP对CD中潘氏细胞缺陷的影响。我们发现AOPP在活动期CD组织中积聚，且与溶菌酶表达呈负相关，而与内质网应激标志物的存在呈正相关。此外，AOPP处理主要通过过度的内质网应激诱导潘氏细胞缺陷，并且AOPP还会导致线粒体相关内质网膜的形成和线粒体功能障碍。此外，内质网应激抑制剂牛磺熊去氧胆酸（TUDCA）的给药可减弱AOPP的作用。这些发现表明AOPP在导致潘氏细胞缺陷方面具有致病作用，并可能为制定治疗CD的新策略提供依据。
