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来自 Pyroptotic 微环境的 HMGB1 促进了 Hirschsprung 相关肠球炎中的巨细胞外陷
Rui Zhang1, Jing Li1, Lili Song2
1Department of Clinical Nutrition, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China.
Advanced biology
|June 4, 2025
概括
巨细胞外陷 (METs) 通过破坏结肠细胞,恶化了与赫斯普隆相关的肠球炎 (HAEC). 高流动性组盒1蛋白 (HMGB1) 驱动METs的形成,这表明它是HAEC的治疗点.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 赫施普隆相关肠道炎 (HAEC) 是赫施普隆病 (HSCR) 的严重并发症.
- 巨细胞外陷 (METs) 涉及炎症性疾病,但它们在HAEC中的作用尚不清楚.
研究的目的:
- 阐明HAEC中METs形成的机制.
- 调查METs在HAEC期间结肠上皮细胞 (CECs) 损伤中的作用.
主要方法:
- 在HAEC模型中研究了METs的形成.
- 分析了高流动性组盒1蛋白 (HMGB1) 和TLR4-p38 MAPK/p65 NF-kB信号的参与.
- 评估了METs对CECs生存能力,反应性氧物种 (ROS) 生产和热的影响.
主要成果:
- 由热性微环境引起的METs形成,加剧了HAEC中的炎症和CEC损伤.
- HMGB1通过TLR4-p38 MAPK/p65 NF-kB通路调解METs的形成.
- 暴露于METs抑制了CEC的生存能力,增加了ROS产量,并诱导了热亡.
结论:
- 在HAEC中,HMGB1将热微环境与METs形成联系起来,放大炎症和CECs损伤.
- 准HMGB1为管理HAEC提供了一个潜在的治疗策略.
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