FoxO3使Smad3诱导的动脉光滑肌细胞生长正常化
Jake T Francisco1, Andrew W Holt1, Michael T Bullock1
1Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
Frontiers in physiology
|September 11, 2023
概括
FoxO3可以逆转Smad3驱动的动脉光滑肌细胞生长,这是心血管疾病的关键因素. 这种涉及特定酸化和细胞局部化的相互作用表明,FoxO3和Smad3是异常ASM生长的潜在治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 细胞信号传输 细胞信号传输
- 分子医学是分子医学.
背景情况:
- 动脉光滑肌 (ASM) 细胞过渡到促进生长的状态是心血管疾病 (CVD) 的核心.
- 转录因子Smad3和FoxO3在ASM生长中的作用尚未完全理解.
- 调查它们的协调影响对于理解心血管疾病的发病过程至关重要.
研究的目的:
- 确定Smad3和FoxO3在控制ASM细胞生长中的协调,酸化特异关系.
- 为了测试FoxO3可以缓解Smad3诱导的ASM细胞生长的假设.
- 探索针对心血管疾病中的Smad3和FoxO3的治疗潜力.
主要方法:
- 使用了老鼠体内动脉损伤模型和体内ASM细胞培养模型.
- 用于Smad3和FoxO3.3过度表达的腺病毒基因传递.
- 分析了蛋白质表达,酸化,细胞局部化和无处不在酶活性 (MuRF-1).
主要成果:
- 在生长条件下,Smad3和FoxO3表现出独特的细胞分布.
- FoxO3的过度表达逆转了Smad3诱导的ASM细胞增殖,Smad3的过度表达逆转了FoxO3诱导的细胞静止.
- FoxO3诱导了MuRF-1的表达,而Smad3的共同表达反转了这种表达,这表明它在调节蛋白质降解方面发挥了作用.
结论:
- FoxO3可以有效地逆转Smad3介导的ASM细胞生长.
- 在Smad3和FoxO3之间存在相互对抗,这取决于酸化和局部化.
- 在心血管疾病中,Smad3和FoxO3代表了减轻ASM异常生长的潜在治疗点.
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