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该CBS/H2S轴调节肠道干细胞稳态和辐射诱导的肠道损伤
Tianyu Wu1,2, Zhiyuan Zheng1, Jiong Ren1
1State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
Stem cell research & therapy
|November 1, 2025
概括
囊氨酸β合成酶 (CBS) /硫化 (H2S) 轴影响肠干细胞 (ISC) 恒常性和辐射敏感性. 通过CBS/H2S通路准非上皮细胞可能为辐射保护提供新的策略.
科学领域:
- 胃肠病学 胃肠病学
- 辐射瘤学 辐射瘤学
- 分子生物学分子生物学
背景情况:
- 肠干细胞 (ISC) 对辐射敏感,可能导致屏障功能障碍.
- 囊氨酸-β-合成酶 (CBS) /硫化 (H2S) 轴参与细胞增殖,DNA损伤反应和反应性氧物种清理.
- 在ISC恒温和组织放射敏感性中,CBS/H2S轴的作用仍然在很大程度上未被探索.
研究的目的:
- 调查CBS/H2S轴在维持肠干细胞 (ISC) 稳态中的作用.
- 为了确定CBS/H2S轴对肠道放射敏感性的影响.
- 探索CBS/H2S轴作为辐射保护战略的目标的潜力.
主要方法:
- 使用Villin-CreERT2和CBSfl/+小鼠生成了特定于肠表皮的有条件的CBS淘汰赛小鼠.
- 使用CAGG-CreERTM和CBSfl/fl小鼠创建了全球CBS淘汰赛小鼠.
- 使用了Lgr5-Tdtaomato-Flag记者小鼠和CRISPR/Cas9.9进行研究.
- 给小鼠和肠道密室有机体注射CBS抑制剂AOAA或H2S供体GYY4137.
- 采用了组织学,免疫组织化学,免疫光,西部斑块和qRT-PCR分析.
主要成果:
- Lgr5+ ISCs和原始细胞显示出比分化的细胞更高的CBS表达,与小肠相比,盲肠和结肠中的CBS水平更高.
- H2S捐赠者GYY4137在体外促进了肠道有机体的增殖,而用AOAA抑制CBS则降低了这种效应.
- 在体内,AOAA治疗减少了辐射诱导的肠粘膜缩,全球CBS降调促进了辐射后ISC恢复.
- 肠表皮特异性CBS淘汰并没有产生辐射保护作用,这表明非表皮细胞的作用.
结论:
- 在CBS/H2S轴影响肠干细胞 (ISC) 恒温.
- 该CBS/H2S轴是辐射保护的潜在治疗目标.
- 由CBS/H2S轴介导的辐射保护可能涉及非上皮细胞相互作用.
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