Inhibition of the Wnt/β-catenin signaling pathway and SOX9 by XAV939 does not alleviate inflammation in a dextran sulfate sodium-induced ulcerative colitis model

The Wnt/β-catenin signaling pathway is known to be hyperactivated during the pathogenesis of ulcerative colitis (UC). The present study aimed to explore the therapeutic efficacy of the Wnt/β-catenin signaling inhibitor XAV939 in mitigating UC symptoms. Utilizing a dextran sulfate sodium (DSS)-induced UC mouse model, the present study aimed to evaluate the impact of XAV939 on intestinal morphology through H&E staining and to measure the expression levels of critical proteins in the Wnt/β-catenin signaling cascade. XAV939 did not exert a significant influence on the morphological features and inflammatory status of the intestinal epithelium. However, XAV939 was found to effectively suppress the Wnt/β-catenin signaling pathway and its downstream target SOX9. This suppression implies a reduction in the differentiation of intestinal stem cells into secretory cell progenitor cells. Additionally, XAV939 was ineffective in reversing the DSS-induced derease in Villin and peroxisome proliferator-activated receptor γ, suggesting that it did not facilitate the differentiation of intestinal absorptive cells. The present findings indicated that the Wnt/β-catenin signaling pathway may not be the predominant mechanism in the pathogenesis of DSS-induced UC. For RNA-sequencing (RNA-seq) experiment, a total of 6 healthy male C57BL/6 mice (18-22 g; 8 weeks of age) were randomly divided into two groups (n=3). The control group received distilled water, while the treatment group received 3.5% DSS for 7 days.