Zhang Xiaofeng, Zuo Lugen, Song Xue, Zhang Wenjing, Yang Zi, Wang Zhiyuan, Guo Yibing, Ge Sitang, Wang Lian, Wang Yueyue, Geng Zhijun, Li Jing, Hu Jianguo
Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China.
iScience. 2024 Dec 1;27(12):111517. doi: 10.1016/j.isci.2024.111517. eCollection 2024 Dec 20.
The hypertrophic mesenteric adipose tissue (htMAT) of Crohn disease (CD) participates in inflammation through the expression of adipokines, but the exact mechanism of this action in the intestine is unknown. Here, we analyzed the expression of secreted frizzled-related protein 5 (SFRP5), an adipokine with cytoprotective effects, in htMAT and its role in CD. The results of this study revealed that the level of SFPR5 increased in the diseased MAT (htMAT) of CD patients and aggregated among intestinal epithelial cells in the diseased intestine and that it could ameliorate intestinal barrier dysfunction in tumor necrosis factor alpha (TNF-α)-stimulated colonic organoids and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced mice at least in part through the inhibition of Wnt5a-mediated apoptosis in epithelial cells. This study elucidates possible mechanisms by which mesenteric adipokines influence the progression of enteritis and provides a new theoretical basis for the treatment of CD via the mesenteric pathway.
克罗恩病（CD）的肥厚性肠系膜脂肪组织（htMAT）通过脂肪因子的表达参与炎症反应，但这种作用在肠道中的具体机制尚不清楚。在此，我们分析了具有细胞保护作用的脂肪因子分泌型卷曲相关蛋白5（SFRP5）在htMAT中的表达及其在CD中的作用。本研究结果显示，CD患者病变的肠系膜脂肪组织（htMAT）中SFRP5水平升高，并聚集在病变肠道的肠上皮细胞之间，且它至少部分通过抑制Wnt5a介导的上皮细胞凋亡，可改善肿瘤坏死因子α（TNF-α）刺激的结肠类器官和2,4,6-三硝基苯磺酸（TNBS）诱导的小鼠的肠道屏障功能障碍。本研究阐明了肠系膜脂肪因子影响肠炎进展的可能机制，并为通过肠系膜途径治疗CD提供了新的理论依据。
