Chronic psychological stress aggravates intestinal barrier damage and promotes enteritis development through inhibiting Wnt/β-catenin pathway
10.3760/cma.j.cn112309-20220802-00256
- VernacularTitle:慢性心理应激抑制Wnt/β-catenin通路加剧肠屏障损伤促进肠炎发展
- Author:
Sha LI
1
;
Zhenzhen RUAN
;
Guangran HU
;
Changqing XU
;
Jing YANG
;
Zhaopeng WANG
;
Wengang SONG
;
Li GE
Author Information
1. 山东第一医科大学第一附属医院（山东省千佛山医院），山东省风湿免疫病转化医学重点实验室，济南 250014
- Keywords:
Chronic psychological stress;
Inflammatory bowel disease;
Intestinal barrier;
Wnt/β-catenin
- From:
Chinese Journal of Microbiology and Immunology
2023;43(1):35-46
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the mechanism by which chronic psychological stress aggravates intestinal barrier damage and promotes the development of enteritis through inhibiting Wnt/β-catenin pathway, so as to provide a new therapeutic strategy for the clinical diagnosis and treatment of inflammatory bowel disease (IBD).Methods:A comorbidity model of chronic psychological stress and enteritis was established using C57BL/6J mice. HE staining was used to analyze the effects of chronic psychological stress on the intestinal pathological damage in mice with enteritis. ELISA was used to detect the expression of proinflammatory cytokines. The ultrastructural changes of colonic cells and the state of intestinal mucus layer were observed under transmission electron microscope and scanning electron microscope. The secretion of mucoprotein 2 (MUC2) and the expression of cell proliferation marker Ki67 were detected by immunofluo rescence staining. The numbers of goblet cells were detected by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Western blot was performed to analyze the expression of tight junction protein between intestinal epithelial cells, β-catenin which was a key protein of Wnt/β-catenin pathway maintaining crypt proliferation, and downstream protein c-myc.Results:The sugar water consumption ratio decreased, but tail suspension immobility time, the swimming immobility time and the expression of corticotropin releasing hormone (CRH) in hypothalamus increased (all P<0.05) in the stress group as compared with those in the control group. Chronic psychological stress promoted weight loss and colonic shortening in mice with enteritis, exacerbated pathological damage and enhanced the release of pro-inflammatory factors. Moreover, increased disappearance of intestinal epithelial microvilli and severe cellular ultrastructural damage were also observed in the stress+ dextran sulfate sodium salt (DSS) group. There was no pathological damage in the control and stress groups. Chronic psychological stress aggravated intestinal barrier injury and inhibited intestinal barrier repair by inhibiting Wnt/β-catenin pathway. Conclusions:In the mouse model of DSS-induced enteritis, chronic psychological stress preconditioning inhibited the Wnt/β-catenin pathway, weakened the repair ability of intestinal epithelium, aggravated the loss of mucus layer of intestinal barrier and the damage of tight junction structure, and promoted the development of enteritis. In the absence of enteritis, chronic psychological stress had no significant effects on the Wnt/β-catenin pathway and the intestinal barrier.
