FTO抑制通过降低ferroptosis激活剂ACSL4和益纤维素因子TGFBI的调节来减轻纤维化
Dalin Zhang1, Chun-Lung Chiu1,2, Ru Wen1
1Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
iScience
|October 6, 2025
概括
向FTO酶可以减少纤维化和铁亡,为由损伤引起的慢性病 (CKD) 提供新的治疗策略.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 病理学 病理学 病理学
背景情况:
- 纤维化 (RF) 是慢性病 (CKD) 的一个关键特征,造成了严重的医疗负担.
- 确定RF的新型治疗点对于管理CKD至关重要.
研究的目的:
- 调查脂肪质量和与肥胖相关的 (FTO) 在纤维化和铁化中的作用.
- 探索FTO抑制作为阻塞相关损伤的潜在治疗策略.
主要方法:
- 使用鼠标模型单边尿路阻塞 (UUO) 和假手术.
- 采用小鼠和人类上皮细胞,以及人类胚胎干细胞衍生的器官.
- 评估了原体沉积,脂质过氧化,铁亡标志物 (例如ACSL4),TGFBI表达和M2巨细胞积累.
主要成果:
- 在UUO小鼠中,FTO抑制显著降低了原沉积,脂质过氧化和铁亡标志物.
- 通过降低ACSL4的调节,减少脂质过氧化和活性氧物种,FTO抑制降低了埃拉斯诱导的铁亡.
- FTO抑制降低了TGFBI的调节,与UUO后的M2巨细胞积累减少相关.
结论:
- 阻断FTO显示出强大的治疗潜力,可以缓解阻塞相关损伤中的纤维化.
- 准FTO可能会降低CKD的患病率,医疗保健成本,并改善患者的生活质量.
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