iScience (Dec 2024)
The mesenteric adipokine SFRP5 alleviated intestinal epithelial apoptosis improving barrier dysfunction in Crohn's disease
Abstract
Summary: 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.