基甲基转移酶G9a驱动了小鼠的血管光滑肌肉细胞增殖和内脏增生
Si-Tong Liu1, Shao-Wei Liu2, Shi-Yi He1
1Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences; National and Local United Engineering Lab of Druggability and New Drugs Evaluation; Guangdong Engineering Laboratory of Druggability and New Drug Evaluation; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, 510006, China.
Acta pharmacologica Sinica
|February 9, 2026
概括
通过调节CEBPδ,G9a促进了血管光滑肌肉细胞的增殖和内脏增生. 抑制G9a为涉及血管改造的心血管疾病提供了潜在的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 血管生物学 血管生物学
背景情况:
- 血管光滑肌细胞 (VSMC) 增殖是心血管疾病中血管重塑的核心.
- G9a (euchromatic histone methyltransferase 2) 是一种涉及表观遗传调节的基因组甲基转移酶.
- 需要阐明G9a在VSMC增殖和血管内皮增生中的作用.
研究的目的:
- 调查G9a在促进VSMC增殖和血管内皮增生中的作用.
- 阐明涉及G9a在这些过程中的潜在分子机制.
主要方法:
- 在实验室中使用血小板衍生的生生长因子-BB (PDGF-BB) 和胎儿牛血清 (FBS) 诱导了VSMC的扩散.
- 血管内皮增生在体内模拟,使用小鼠动脉绑定.
- 使用抑制剂UNC0642和G9a腺病毒调节G9a活性;通过RNA-seq和ChIP测定确定下游目标.
主要成果:
- 在体外和体外VSMC增殖模型中,G9a表达显著升高.
- 抑制G9a降低了VSMC的活力,扩散 (EDU的结合) 和环林D1的表达.
- 在体内,G9a抑制减少了亲密区域,而G9a过度表达加剧了增生症.
- 发现G9a通过H3K9me1在其促进体上的修饰来调节CCAAT/增强剂结合蛋白三角形 (CEBPδ) 表达.
结论:
- G9a作为VSMC增殖和血管内皮增生的积极调节者.
- G9a通过下游目标CEBPδ.部分调解其影响.
- G9a代表了由血管重塑为特征的心血管疾病的潜在治疗点.
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