心理压力诱导的系统性皮质直接破坏肠道干细胞,并加剧结肠炎
Xiaole Sheng1, Lanfei Jin1, Zhengrong Yao1,2,3
1Department of General Surgery, Sir Run Run Shaw Hospital and Institute of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Cell discovery
|May 13, 2025
概括
心理压力会减少肠道干细胞数量和通过大脑-肠轴的增殖. 慢性压力会增加皮质,损害干细胞功能,恶化结肠炎.
科学领域:
- 胃肠病学 胃肠病学
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
背景情况:
- 心理压力通过大脑-肠轴影响胃肠道.
- 压力对肠道干细胞 (ISC) 的特定影响及其在维持肠道平衡中的作用尚未完全理解.
研究的目的:
- 研究慢性心理压力对肠道干细胞的影响.
- 阐明压力影响ISC数量,增殖和功能的分子机制.
- 为了确定ISC功能障碍对压力加剧的肠炎的贡献.
主要方法:
- 在慢性压力模型中评估ISC数量和扩散.
- 测量了皮质水平和下丘脑-垂体-上腺 (HPA) 轴的激活.
- 研究了核受体亚家族3组c成员1 (NR3C1) 和FKBP prolyl isomerase5 (FKBP5) 在ISC中的作用.
- 分析了AKT和分叉盒O (FoxO) 信号通路.
- 评估了压力对硫酸 (DSS) 诱导的大肠炎的影响.
主要成果:
- 慢性压力显著降低了ISC数量和繁殖能力.
- 由于HPA轴激活,皮质水平升高是ISC减少的原因.
- 皮质类固醇通过NR3C1.1直接增加了ISC中的FKBP5表达.
- 通过促进AKT脱和FoxO核转移,FKBP5抑制了ISC的扩散.
- ISC功能障碍加剧了DSS诱导的大肠炎.
结论:
- 心理压力会通过涉及皮质的脑至肠道途径损害肠道干细胞活动.
- 这种机制解释了压力如何增加对结肠炎的易感性.
- 研究结果揭示了一种新的调节途径,影响压力下肠道平衡.
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