移植中的核素1乳化会诱导ferroptotic触发波,加剧延迟的移植功能
Haitao Yu1,2,3, Hubin Yin1,3, Yuhua Mei1,3
1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
Nature communications
|December 5, 2025
概括
铁波使损伤恶化,并延迟了移植功能. 向核胺1 (NPM1) 乳化,这是一个代谢-表观遗传过程,可以防止铁灭菌的传播,并改善移植的功能.
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
- 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:
- 铁波会加剧缺血-再输液损伤 (IRI),并导致移植功能延迟 (DGF).
- 在受伤的移植中,糖解和乳酸生产的增加与铁亡和功能障碍有关.
研究的目的:
- 为了阐明驱动脏IRI中的ferroptotic传播的分子机制.
- 确定缓解DGF的治疗目标.
主要方法:
- 乳酸组的分析,以识别乳酸蛋白质.
- 研究了长非编码RNA (lncRNA) IGIP-5,microRNA 670-3p和乳酸脱酶A (LDHA) 信号轴的作用.
- 利用小鼠脏全移植模型和体外细胞培养系统.
- 开发了一种使用尿液中乳酸盐水平的DGF预测模型.
主要成果:
- 一个涉及IGIP-5,microRNA 670-3p和LDHA的信号轴促进乳酸分泌,诱导邻近细胞中的乳酸和铁亡.
- 核胺1 (NPM1) 被AARS1在K257中乳化,稳定NPM1并增强SLC7A11的抑制,这扰乱了囊的新陈代谢并促进了铁亡.
- 抑制NPM1乳化 (通过K257突变,AARS1淘汰赛或taurochenodeoxycholic酸) 调节SLC7A11并降低铁亡.
- 阻断乳酸穿介导的NPM1乳化在小鼠中,通过防止ferroptosis传播改善了移植功能.
- 手术后的尿乳酸度可以预测DGF.
结论:
- 一个新的代谢-表观遗传轴,涉及乳酸诱导的NPM1乳化,驱动脏IRI中的ferroptotic传播.
- NPM1乳化是铁和囊代谢的关键调节者.
- 向NPM1乳化为DGF提供了一个有前途的治疗策略.
- 尿液中的乳酸盐水平为早期DGF预测提供了潜在的生物标志物.
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