在膀光滑肌细胞中,EZH2和矩阵共同调节表型和KCNB2的表达
Priyank Yadav1,2, Tabina Ahmed1, Suejean Park1
1The Hospital for Sick Children Toronto, Ontario, Canada.
American journal of clinical and experimental urology
|August 30, 2023
概括
部分膀输出阻塞 (PBO) 改变了表观遗传标记,特别是增加了KCNB2基因促进体中的H3K27me3. 这种表观遗传失调影响光滑肌肉细胞表型,提供潜在的治疗点.
科学领域:
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 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
背景情况:
- 部分膀输出阻塞 (PBO) 导致尿功能障碍和大量的医疗保健费用.
- 以前的研究将阻塞与改变的表观遗传调节和细胞功能联系起来.
- 这项研究调查了PBO和慢性膀阻塞性疾病 (COBD) 的表观遗传变化.
研究的目的:
- 为了检查PBO和COBD是否影响原则证明基因中的表观遗传标记.
- 探索膀光滑肌细胞 (SMC) 中表观遗传调节的机制.
主要方法:
- 老鼠接受了手术绑定以模拟PBO和COBD,以假绑定作为对照.
- 使用免疫染和ChIP/PCR评估了Histone3 lysine27三甲基化 (H3K27me3).
- 在体外研究中,在不同的矩阵上使用人体膀SMC,用EZH2抑制剂 (UNC1999) 处理,并分析KCNB2,H3K27me3和细胞表型.
主要成果:
- 在PBO和COBD期间,KCNB2促进区的H3K27me3水平增加.
- 与假冒程序相比,阻塞导致H3K27me3沉积增加.
- 在体外,EZH2抑制恢复了KCNB2表达和部分正常化的SMC表型.
结论:
- 在阻塞过程中,KCNB2基因调节显示了动态的H3K27me3变化.
- 试验室模型表明,矩阵相互作用影响EZH2,H3K27me3和KCNB2调节.
- 这些表观遗传机制可以在体内控制光滑肌肉细胞表型.
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