长非编码RNA TUG1通过KLF4-肌肉细胞轴调节平滑肌肉细胞分化
Ravi Abishek Bharadhwaj1,2, Regalla Kumarswamy1,2
1CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Telangana, India.
American journal of physiology. Cell physiology
|August 29, 2023
概括
长非编码RNA TUG1在腹腔大动脉动脉瘤 (AAA) 中被上调,并通过与KLF4相互作用来驱动光滑肌细胞 (SMC) 功能障碍,影响AAA发育.
科学领域:
- 血管生物学 血管生物学
- 分子遗传学 分子遗传学
- 非编码RNA研究研究
背景情况:
- 腹腔大动脉瘤 (AAA) 是危及生命的血管疾病,与光滑肌肉细胞 (SMC) 功能障碍有关.
- 长非编码RNAs (lncRNAs) 在SMC功能障碍和AAA病变发生中的作用在很大程度上尚未被探索.
研究的目的:
- 调查lncRNA TUG1在SMC功能障碍中的作用及其对AAA发展的贡献.
- 阐明TUG1在血管素II诱导的AAA中的调节机制.
主要方法:
- 在接受 angiotensin-II 治疗的 SMC 和小鼠 AAA 模型中进行 lncRNA 分析.
- 通过促进物 luciferase 和 ChIP 试验研究了 TUG1 转录调节.
- 进行了体外功能增益/丧失实验和免疫沉试验.
主要成果:
- 在SMC和小鼠AAA模型中,TUG1在接受血管新生素II治疗后被上调.
- TUG1是Notch路径的直接转录标,其表达与SMC收缩基因相反相关.
- TUG1的过度表达抑制了SMC的分化;通过与KLF4相互作用来抑制肌肉激素,Knockdown增强了它.
结论:
- lncRNA TUG1在AAA发育中的SMC功能障碍中起着关键作用.
- TUG1通过KLF4-心肌轴调节SMC分化,这代表了AAA的潜在治疗标.
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