通过IGF1R,CircDiaph3通过调节PI3K/AKT/mTOR通路来影响PASMC亡
Ge Liu1, Shengqiang Zhang1, Shaofeng Yang1
1Department of Cardiac Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui People's Republic of China.
3 Biotech
|September 14, 2023
概括
循环RNAcircDiaph3促进肺动脉平滑肌肉细胞的增殖和迁移,导致肺高血压. 抑制circDiaph3可能为这种情况提供一种新的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 在RNA生物学,RNA生物学.
背景情况:
- 肺高血压 (PH) 的发病原因尚不清楚.
- 肺动脉光滑肌肉细胞 (PASMC) 增殖是PH的一个关键特征.
- 循环RNAs (circRNAs) 正在成为心血管疾病的关键调节者.
研究的目的:
- 调查circDiaph3在PH中的作用.
- 阐明 circDiaph3 在 PASMC 中的功能背后的分子机制.
- 在PH模型中评估circDiaph3抑制的治疗潜力.
主要方法:
- 实时定量PCR分析患者样本中的circDiaph3表达.
- 建立低氧性肺动脉高血压 (PAH) 的老鼠模型.
- 在大鼠PASMC和体内研究中,通过小干扰RNA (siRNA) 介导的circDiaph3的淘汰.
主要成果:
- 在PH患者中,CircDiaph3过度表达.
- 在CircDiaph3 Knockdown下调PI3K/AKT/mTOR和IGF1R信号通路以及光滑肌细胞标记物 (α-SMA,Vcam1).
- 过度表达IGF1R挽救了这些效应,促进了PASMCs的增殖和减少了apoptosis. 在生体内抑制circDiaph3改善了大鼠的PAH.
结论:
- 通过PI3K/AKT/mTOR/IGF1R信号轴,CircDiaph3调节了PASMC的增殖和亡.
- 过度的PASMC增殖有助于肺动脉光狭窄和PH.
- CircDiaph3代表了肺高血压的潜在治疗标.
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