《肝脏BMAL1和HIF1α调节时间依赖性低氧反应并预防肝肺样综合征》

  • 编译者: 黄雅兰
  • 发布时间:2024-09-29
  • 对低氧的转录反应是暂时调节的,但其分子基础和生理意义尚不清楚。我们研究了肝脏Bmal1和Hif1α在小鼠缺氧昼夜反应中的作用。我们发现大多数对缺氧的转录反应依赖于Bmal1或Hif1α,通过白天决定的共享和不同的作用。我们进一步表明缺氧诱导因子(HIF)1α在缺氧时的积聚是暂时调节的,并且是Bmal1依赖性的。出乎意料的是,缺乏肝脏Bmal1和Hif1α的小鼠缺氧,并在缺氧暴露时以日间依赖的方式表现出死亡率增加。这些小鼠表现出轻度肝功能障碍,肺血管扩张,可能是由于细胞外信号调节激酶(ERK)激活、内皮型一氧化氮合酶和一氧化氮在肺中积聚,提示肝肺综合征。我们的发现表明,肝脏BMAL1和HIF1α是低氧反应的关键时间依赖性调节因子,可以为肝肺综合征的病理生理学提供分子水平的见解。
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