升高的FTO通过调节巨细胞炎症表型来缓解败血症引起的急性损伤
Xiaona Chen1, Ziqi Sun2, Jiabo Chen2
1School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518055, P.R. China.
International journal of molecular medicine
|November 14, 2025
概括
脂肪质量和与肥胖相关的蛋白质 (FTO) 在败血症引起的急性损伤 (SAKI) 中降低. 恢复FTO水平通过准矩阵金属蛋白酶9 (MMP-9) 来减少炎症和损伤.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 腎臟病學 (nephrology) 是一種醫學.
背景情况:
- 败血症诱导的急性损伤 (SAKI) 涉及失调的N6-甲基氨酸 (m6A) 修饰,导致过度炎症和器官损伤.
- 脂肪质量和与肥胖相关的蛋白质 (FTO) 是一种m6A脱甲基酶,涉及各种生物过程.
- 识别SAKI中的关键分子调节剂对于开发有效的治疗策略至关重要.
研究的目的:
- 调查FTO及其相关的m6A通路在SAKI中的作用.
- 阐明FTO在败血症期间影响炎症和损伤的分子机制.
- 探索SAKI中针对FTO/m6A轴的治疗潜力.
主要方法:
- 来自败血症患者的转录基因数据集 (GSE32707,GSE69063) 的生物信息分析.
- 在实体研究中,使用小鼠的结和穿孔 (CLP) 模型来评估脏组织和腹巨细胞中的FTO表达和m6A修饰.
- 在体外实验中使用脂聚糖 (LPS) 刺激的巨细胞来评估FTO对细胞因子产生和MMP-9转化的影响.
- 多原子分析以确定FTO的直接目标.
主要成果:
- 在败血症患者的周围血液和败血症小鼠的脏和巨细胞中,FTO显著下调.
- 增加的FTO水平与败血症小鼠的死亡率和损伤降低相关.
- 在巨细胞中FTO的升级降低了前炎性细胞因子的产生.
- 确定了矩阵金属蛋白酶9 (MMP-9) 作为FTO的直接翻译标.
- 在体内和体外模型中,降低的MMP-9水平加剧了炎症反应和损伤.
结论:
- 在SAKI期间,FTO/m6A/MMP-9轴在调节促炎性细胞因子分泌中发挥着关键作用.
- 通过增加MMP-9翻译,FTO下调有助于性败血症中的损伤.
- 向FTO/m6A/MMP-9通路是一个有希望的治疗策略,可以缓解败血症中的损伤.
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