关键词: 幼年性息肉综合征家系, SMAD4, 转化生长因子-β

Abstract: Objective To investigate the molecular mechanisms underlying the pathogenesis of juvenile polyposis syndrome (JPS) in a family.Methods Eight family members of a JPS family were enrolled,and polyp tissue samples were collected for HE staining and immunohistochemical analysis.Results SMAD4 mutation led to a significant reduction in protein expression,and the activity of phosphorylated SMAD3,a key molecule in the downstream TGF-β signaling pathway,was significantly weakened,resulting in glandular structural disorder,infiltration of inflammatory cells,and epithelial atypia.Moreover,Bax expression was upregulated in both the mutated tissue and the control group.Bcl-2 showed consistently elevated expression in the mutant group,while maintaining normal or decreased expression in the control group.Caspase3 exhibited reduced expression in the mutant group,with normal expression levels observed in the control group.Conclusion The SMAD4 mutation promotes the formation of JPS lesions through disruption of the TGF-β signaling pathway and apoptosis regulation imbalance.These findings provide new insights for the early diagnosis and targeted therapy of the disease.

Key words: juvenile polyposis syndrome family, SMAD4, transforming growth factor-β