定量蛋白质学将线粒体功能障碍与高氧暴露新生儿气道细胞中的代谢变化和上皮分化缺陷联系起来
bioRxiv : the preprint server for biology
|July 15, 2025
概括
暴露于高氧水平会通过破坏线粒体,损害早产婴儿的气道细胞发育. 这种代谢功能障碍阻碍了粘膜分化,可能导致肺损伤.
科学领域:
- 新生儿呼吸系统研究新生儿呼吸系统研究
- 线粒体生物学 线粒体生物学
- 皮质细胞分化的表皮细胞分化.
背景情况:
- 补充氧气对于早产婴儿至关重要,但可能导致肺部损伤.
- 过氧诱导的支气管肺功能障碍与线粒体功能障碍有关.
- 过氧对上呼吸道上皮质发育和线粒体的影响尚不清楚.
研究的目的:
- 调查高氧化是否会损害新生儿呼吸道粘膜分化.
- 为了确定线粒体生物能功能障碍是否介导这种损伤.
主要方法:
- 在3D空气-液体接口模型中培养的新生儿气管上皮细胞.
- 在分化过程中暴露于60%的氧气.
- 评估细胞表型,线粒体功能 (海马分析) 和蛋白质表达 (蛋白质组学).
主要成果:
- 过氧症减少了纤毛细胞和杯状细胞的形成,损害了分化.
- 线粒体的氧气消耗和ATP的产生减少;糖解增加.
- 蛋白质组学揭示了线粒体复合体I的干扰和改变的NOTCH/TGF-β信号传递.
结论:
- 适度的过氧症会破坏线粒体的生物能量和代谢编程.
- 这导致新生儿呼吸道上皮质的粘膜分化受损.
- 线粒体功能是新生儿肺损伤的潜在治疗点.
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