抑制性H3K27me3驱动人体内皮质中高血糖引起的氧化和炎症转录程序
Julia Sánchez-Ceinos1, Shafaat Hussain1,2, Abdul Waheed Khan1,3
1Cardiology Unit, Department of Medicine-Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Cardiovascular diabetology
|April 5, 2024
概括
由EZH2驱动的素H3氨酸27三甲基化 (H3K27me3),促进高血糖引起的氧化应激和内皮细胞的炎症. 准EZH2可能会预防与糖尿病相关的血管疾病.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 血管生物学 血管生物学
背景情况:
- 基因组蛋白修饰调节了健康和疾病中的基因表达.
- 基因组甲基转移酶 (EZH1,EZH2) 和脱甲基酶 (UTX,JMJD3,UTY) 控制H3K27me3的水平.
- 这项研究调查了H3K27me3在高血糖引起的内皮氧化和炎症反应中的作用.
研究的目的:
- 为了确定H3K27me3是否会在内皮细胞中触发高血糖诱导的氧化和炎症转录程序.
- 阐明EZH2和H3K27me3在内皮功能障碍中的作用.
- 探索针对EZH2.2的治疗潜力.
主要方法:
- 使用了人类大动脉内皮细胞 (HAEC) 和来自糖尿病患者的细胞 (D-HAEC).
- 雇佣的RT-qPCR,免疫阻塞,ChIP-qPCR,共聚焦显微镜和ESR光谱.
- 在db/db小鼠大动脉中研究的效果和使用的药理 EZH2 抑制 (GSK126).
主要成果:
- 在HAEC中,高葡萄糖通过EZH2上调和UTX/JMJD3下调增加了H3K27me3.
- H3K27me3抑制了超氧化物脱酶和JunD,促进了NOX4表达和氧化应激.
- H3K27me3增强了NF-κB活性和炎症基因表达;GSK126扭转了这些影响.
- 在D-HAEC和db/db小鼠大动脉中观察到类似的表观遗传变化.
结论:
- EZH2介导的H3K27me3是高血糖引起的内皮功能障碍的关键表观遗传驱动因素.
- 准EZH2可以减少氧化应激和炎症.
- 这表明EZH2抑制是预防糖尿病血管并发症的策略.
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