结肠炎症的性别差异是由雌激素受体α的表皮特异性表达驱动的
Guillermo A Pereda1, Adrian D Kocinski1, Alyssia V Broncano1
1Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Gastro hep advances
|April 29, 2025
概括
雌激素受体α (ERα) 在肠道中发出信号,在男性和女性中具有相反的效果. 删除ERα保护女性免受肠道损伤,但在男性中使其恶化,揭示了性别特异性机制.
科学领域:
- 内分泌学 在内分泌学.
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
背景情况:
- 炎症性肠病 (IBD) 与雌激素受体 (ERα,ERβ) 和GPER1表达的改变有关.
- 以前的研究表明,ERα删除可以保护雌性小鼠免受肠道损伤,但机制尚不清楚.
- 这项研究研究了ERα和ERβ在肠道上皮功能中的性别特异性作用.
研究的目的:
- 为了比较男性和女性肠道上皮细胞中的ERα和ERβ特异性机制.
- 阐明雌激素受体对肠道健康和疾病的性别影响.
主要方法:
- 在小鼠结肠细胞中评估了ERα,ERβ,GPER1和Cyp19A1的表达.
- 生成的肠上皮细胞 (IEC) 特定的ERα和ERβ淘汰赛小鼠.
- 使用硫酸德克斯 (DSS) 诱导结肠炎和结肠器官,用于机械研究.
主要成果:
- 大肠细胞表达ERα,ERβ,GPER1和产生雌激素的Cyp19A1.1.
- 具有IEC特异性ERα淘汰的雌性小鼠受到DSS诱导的大肠炎的保护;雄性小鼠表现出恶化的病理.
- 雄性ERα-Knockout有机体表现出增加的增殖和功能基因表达的减少,而雌性ERα-Knockout有机体表现出保护性特征.
结论:
- 在IEC中,ERα信号传递对肠表皮的发育,再生和炎症产生相反的,取决于性别的作用.
- 这些发现凸显了ERα在性别特异性肠上皮反应和IBD易感性方面的关键作用.
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