PGK1乳化驱动的自我强化循环在FSP1+巨中调节糖溶性重编程肝纤维化
Min Tang1, Mengxue Sun1, Hui Zhang2
1Department of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Research (Washington, D.C.)
|March 5, 2026
概括
研究人员发现了一种新的FSP1+巨细胞通路,通过增强的葡萄糖分解和乳糖化驱动肝纤维化. 在临床前模型中,通过一种新来向这种途径有效地减少了纤维化进展.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢重编程是一种代谢重编程.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 肝纤维化治疗是有限的,代谢和表观遗传因素起着关键作用.
- 乳酸中介乳酸化对肝脏微环境的具体贡献尚未完全理解.
研究的目的:
- 为了确定肝纤维化的新型治疗点.
- 阐明乳酸介导乳酸化在纤维化进展中的作用.
- 在代谢-免疫交叉中研究FSP1-糖解-乳化轴.
主要方法:
- 公共数据库和人肝硬化组织的综合分析.
- 骨髓细胞特定的Fsp1淘汰赛小鼠模型.
- 蛋白相互作用 (FSP1-PKM2) 和翻译后修饰 (PGK1乳化) 的机制性研究.
- 开发和测试一种透细胞的,向PGK1乳化.
主要成果:
- 一个致病性FSP1+巨细胞子集被确定为一个关键的治疗标.
- 发现了FSP1-糖解-乳化轴,推动了纤维化的进展.
- FSP1稳定了巨细胞中的PKM2,增强了糖解和乳酸生产.
- 在K353中对PGK1的KAT2B依赖的乳化产生了正反循环,放大了糖解.
- 一个向PGK1-K353的酸乳化减弱了肝纤维化进展.
结论:
- 乳酸介导的PGK1乳酸化是纤维化新陈代谢的一个关键节点.
- FSP1-糖解轴维持了亲纤维的微环境.
- 向PGK1-K353乳化为慢性肝病提供了一个有前途的治疗策略.
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