载体ZIP12调节肺血管对慢性缺氧的反应
Lan Zhao1, Eduardo Oliver1, Klio Maratou2
1Centre for Pharmacology and Therapeutics, Division of Experimental Medicine, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
Nature
|August 11, 2015
概括
研究人员确定载体ZIP12 (Slc39a12) 是低氧引起的肺高血压的关键因素. 抑制ZIP12可能为这种疾病提供新的治疗策略.
科学领域:
- 生理学 生理学 生理学
- 遗传学 遗传学 是一个
- 药理学 药理学是指药理学的学科.
背景情况:
- 哺乳动物的肺循环在氧气不足的情况下通常会收缩和重塑,导致肺高血压和右心室缩.
- 一些哺乳动物对缺氧诱导的肺高血压具有遗传抵抗力,这表明了潜在的调节机制.
研究的目的:
- 确定调节缺氧诱导的肺血管改造的遗传因素.
- 研究载体ZIP12在肺高血压中的作用.
主要方法:
- 在老鼠的先天性育种计划和比较基因组学.
- 在敏感的哺乳动物物种 (老鼠,奶牛,人类) 中分析ZIP12表达.
- 在肺血管平滑肌细胞的体外研究和在缺氧大鼠的体内研究.
主要成果:
- 编码为ZIP12的Slc39a12被确定为缺氧诱导的肺血管重塑的主要调节者.
- 敏感哺乳动物的肺动脉小动脉中ZIP12的表达增加,并且在光滑肌肉细胞中依赖于缺氧.
- 抑制ZIP12降低了细胞内和光滑肌肉细胞的增殖;基因干扰减轻了大鼠的肺高血压.
结论:
- ZIP12在哺乳动物肺血管恒温中发挥着根本性的作用.
- 准ZIP12为治疗肺高血压提供了一种新的治疗方法.
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