STAT3和HIF1α合作调解转录和生理反应对缺氧的反应
Alberto Dinarello1, Riccardo Massimiliano Betto2, Linda Diamante2
1Department of Biology, University of Padova, Padova, Italy.
Cell death discovery
|July 5, 2023
概括
信号转换器和转录3激活器 (STAT3) 对缺氧诱导的基因表达和血管生成等生理过程至关重要. STAT3与低氧诱导因子1-alpha (HIF1α) 物理相互作用,调节细胞功能必不可少的特定基因子集.
科学领域:
- 细胞生物学 细胞生物学
- 分子机制的分子机制
- 生理学调节是指生理学调节.
背景情况:
- STAT3和HIF1α是细胞过程中的关键转录因子.
- 已知它们在病理条件下的相互作用,但机制和生理相关性尚不清楚.
- 了解STAT3在低氧反应中的作用至关重要.
研究的目的:
- 在小鼠胚胎干细胞 (ESC) 中识别由STAT3调节的缺氧诱导基因.
- 研究STAT3-HIF1α相互作用的分子机制.
- 用斑马鱼模型确定STAT3在低氧反应中的生理作用.
主要方法:
- 在斑马鱼中进行CRISPR/Cas9基因编辑,以创建一个stat3淘汰线.
- 对小鼠ESC中缺氧诱导的基因表达的分析.
- 使用低氧斑马鱼记者线 (HRE:mCherry).
主要成果:
- 对于特定的缺氧诱导基因 (例如Vegfa,Hk1,Hk2) 的转录,需要STAT3.
- 缺少STAT3不会影响Hif1αmRNA或蛋白质水平,这表明转录后调节.
- 在物理上,STAT3与HIF1α相互作用,以调节缺氧依赖基因.
- STAT3激活,特别是Y705酸化,对于体内低氧反应至关重要.
- 通过STAT3切除,可以防止缺氧诱导的血管化,血管生成和免疫细胞调动.
结论:
- STAT3通过与HIF1α的物理相互作用来调节特定的低氧诱导基因子集.
- STAT3在生理缺氧反应中发挥着关键的,非正规的作用,包括血管新生和免疫细胞功能.
- STAT3的Y705酸化是其在缺氧信号传递中的关键作用.
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