在内皮-介质酶过渡中BMP2和Notch信号之间的相互作用:对心脏纤维化的影响
Pavel Docshin1,2, Ahmad Bairqdar2, Anna Malashicheva2
1Laboratory of Molecular Cardiology, Institute of Molecular Biology and Genetics, Almazov National Medical Research Centre, Saint Petersburg, Russia.
诺奇和骨形态遗传蛋白2 (BMP2) 途径共享调节内皮细胞转移到介质细胞转变 (EndoMT) 的目标. 它们的平衡影响心脏纤维化,这表明心力衰竭的新治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 细胞信号传输 细胞信号传输
- 发展生物学 发展生物学
背景情况:
- 在心脏发育和疾病中,内皮细胞转移至介质细胞转换 (EndoMT) 是至关重要的.
- 心脏纤维化是心力衰竭的标志,涉及到原沉积和重塑.
- 胚胎途径,包括骨形态遗传蛋白2 (BMP2) 和Notch,调节EndoMT,但它们的相互作用尚不清楚.
研究的目的:
- 调查Notch和BMP2信号的下游目标.
- 确定它们在心脏介质细胞 (CMC) 和人静脉内皮细胞 (HUVEC) 中对EndoMT标记物的联合作用.
主要方法:
- 细胞培养 (CMC和HUVEC) 被转化为表达NOTCH1细胞内域 (NICD) 和/或BMP2的载体.
- 评估了基因表达和EndoMT标记物的激活.
主要成果:
- 诺奇和BMP2信号通道表现出共同的下游目标,影响EndoMT.
- 途径的激活取决于细胞类型.
- 共同培养的CMC和HUVEC导致基因表达和α-平滑肌肉活性蛋白 (α-SMA) 合成的细胞反应相反.
结论:
- 诺奇和BMP2信号之间的相互作用极大地影响了EndoMT和心脏纤维化.
- 对诺奇-BMP2相互作用的进一步研究是针对心脏纤维化治疗新治疗策略的必要.
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