在共同培养模型中,初级膜限制了TGF-β/SMAD信号传导诱导的RIBEs
Pei Qu1, Yuan Wang1, Zhi'ang Shao1
1Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Space Radiobiology of Gansu Province & Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.
Cellular signalling
|May 24, 2025
概括
主要毛 (PC) 限制转化生长因子β (TGF-β) 信号传输,从而调节辐射诱导的旁观者效应 (RIBEs). PC 抑制会加剧DNA 损伤并抑制其增殖,突出显示了 PC 的作用.
科学领域:
- 细胞生物学 细胞生物学
- 辐射生物学 辐射生物学
- 分子信号传输的方法
背景情况:
- 转化生长因子β (TGF-β) 是细胞对电离辐射反应的关键细胞因子,包括辐射诱导的旁观者效应 (RIBEs).
- 主 (PC) 是关键的细胞器官,调节多种信号通路,包括TGF-β信号,并与细胞对辐射的反应有关.
- 以前的研究表明,PC通过限制TGF-β信号传递来调节RIBEs.
研究的目的:
- 调查一次性眼 (PC) 在调节辐射诱导的旁观者效应 (RIBEs) 中的机械作用.
- 阐明TGF-β信号传导和DNA损伤反应途径在PC介导的RIBEs调节中的参与.
主要方法:
- 采用了共培养旁观者系统的质子微束辐射 (MR) 和部分辐射 (PR) 模型.
- 使用siRNA调节PC形成并抑制DNA损伤反应激酶 (ATM,ATR,DNApk).
- 量化γH2AX焦点,细胞增殖和反应性氧/物种 (ROS/NO) 水平.
主要成果:
- 在PR和MR模型中,PC抑制显著增加了γH2AX焦点并抑制了细胞增殖,而TGF-β抑制则逆转了这种效应.
- 抑制ATM,ATR或DNApk减少了γH2AX焦点,但也减少了增殖;清除ROS/NO减弱了DNA损伤并提高了生存率.
- 在PC缺乏细胞中的SMAD2/3抑制降低了ATM/ATR和降低了NO/ROS,表明TGF-β1通过规范信号传递驱动RIBEs相关的DNA损伤.
结论:
- TGF-β1通过规范的p-SMAD2/3信号传导驱动RIBEs相关的DNA损伤,放大ROS/NO的产生和过度激活DNA损伤反应激酶.
- 主要毛 (PC) 在缓解辐射诱导旁观者效应 (RIBEs) 进展期间的DNA损伤方面发挥着至关重要的调节作用.
- 电脑细胞限制TGF-β信号传递,从而限制DNA损伤的放大和旁观细胞中的增殖抑制.
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