综合机器学习和实验验证确定FIS1作为与肺高血压中的线粒体动力学相关的候选生物标志物
Yu Zhang1,2, Qing Dai2,3, Lijun Gong2,3
1School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
Cells
|February 12, 2026
概括
这项研究揭示,增加FIS1表达驱动肺高血压 (PH) 通过引起线粒体碎片化和肺动脉光滑肌细胞中的铁亡,有助于血管重塑.
科学领域:
- 线粒体生物学 线粒体生物学
- 心血管研究的心血管研究.
- 分子病理学分子病理学
背景情况:
- 肺高血压 (PH) 涉及复杂的肺血管改造,治疗方法有限.
- 线粒体动力学与PH病原发生有关,但关键调节者尚未定义.
研究的目的:
- 识别和功能性地描述调节PH中线粒体动态的基因.
- 探索已识别的基因在肺动脉光滑肌细胞 (PASMC) 功能障碍和PH中的作用.
主要方法:
- 集成的转录基因数据与线粒体注释.
- 使用WGCNA和机器学习优先考虑候选基因.
- 在低氧诱导的PH小鼠模型和培养小鼠PASMCs (mPASMCs) 中使用分子和细胞测定验证的结果.
主要成果:
- 确定了FIS1作为与PH相关的关键基因,显示了高的歧视性表现.
- 缺氧增加了FIS1的表达,导致线粒体碎片化,膜潜能损失,并在mPASMCs中积累ROS.
- 抑制FIS1 knockdown抑制了mPASMC的增殖和迁移,减少了线粒体损伤,并减轻了铁亡.
结论:
- FIS1通过线粒体裂变和铁亡促进PH病原,促进异常的PASMC表型和血管重塑.
- 这项研究为PH的线粒体通路提供了机制性见解和潜在的治疗点.
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