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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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE275191 | GEO | 2024/08/23

REPOSITORIES: GEO

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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

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