在性结肠炎中,HMGB1通过抑制Cpt1a表达来调节巨代谢和极化
Fenfen Wang1, Linfei Luo1, Zhengqiang Wu1
1Department of Gastroenterology, Second Affiliated Hospital of Nanchang University, 330006 Nanchang, Jiangxi, China.
Frontiers in bioscience (Landmark edition)
|November 30, 2024
概括
高流动性组盒-1蛋白 (HMGB1) 通过促进M1巨细胞通过代谢重编程的极化驱动性结肠炎 (UC). 抑制HMGB1可以减少UC症状和炎症,这表明HMGB1是治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
背景情况:
- 大细胞两极分化是性结肠炎 (UC) 发展的关键因素.
- 高流动性组盒-1蛋白 (HMGB1) 涉及UC病变发生.
研究的目的:
- 研究HMGB1如何通过UC的代谢重编程调节巨细胞极化.
- 阐明HMGB1在UC病变发生过程中的作用机制.
主要方法:
- 在使用硫酸 (DSS) 的小鼠中诱导大肠炎.
- 极化巨细胞 (M1/M2) 在体外和评估透在体内.
- 评估细胞代谢 (糖解,粮农组织) 和炎症标志物.
- 通过ChIP和光酶试验,研究了卡尼丁棕转移酶1A (Cpt1a) 表达的HMGB1调节.
主要成果:
- 在UC模型小鼠中,HMGB1和巨细胞透率升高.
- HMGB1的过度表达促进了M1的两极分化,增加了糖解,减少了脂肪酸氧化 (FAO).
- HMGB1的淘汰促进了M2的两极分化,减少了糖解,增加了FAO,对Cpt1a的表达产生了负面调节.
- 在体内,AAV介导的HMGB1敲击改善了UC症状和炎症.
结论:
- Cpt1a表达的HMGB1抑制驱动M1巨细胞极化和UC进展.
- 针对HMGB1提供了性结肠炎的潜在治疗策略.
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