心肌细胞YAP抑制心肌炎症和纤维化,并抑制MEF2调节的基因表达
Van K Ninh1,2, Melissa Barlow1, Sidar Aydin1,3
1Department of Pharmacology, University of California San Diego School of Medicine, La Jolla, CA 92093.
概括
心肌细胞中的YES相关蛋白 (YAP) 途径通过抑制MEF2调节基因来抑制炎症. 删除YAP会加剧炎症反应和心脏功能障碍,强调YAP.
科学领域:
- 心血管生物学 心血管生物学
- 分子心脏病学分子心脏病学
- 转录条例 转录条例 转录条例
背景情况:
- 通过YES相关蛋白 (YAP) 传递心肌细胞信号,可以保护心脏应激.
- 心肌细胞中的炎症反应对于发展心脏功能障碍至关重要.
研究的目的:
- 研究心肌细胞中YAP和炎症基因表达之间的关系.
- 阐明YAP在心脏压力期间调节炎症反应中的作用.
主要方法:
- 使用心肌细胞特异性YAP-knockout (YAP-KO) 小鼠和野生类型 (WT) 的 littermates.
- 给小鼠和分析心脏组织的安吉奥素II (AngII) 输液.
- 进行了单核RNA测序 (snRNA-seq) 和西部斑分析.
- 在孤立心肌细胞中进行siRNA转染.
主要成果:
- 在心肌细胞中,YAP删除显著增强了AngII诱导的炎症性细胞因子和化学因子mRNA表达的选择性.
- 在YAP-KO心脏中,snRNA-seq揭示了促炎基因,cJun家族,CamKIIδ和Tlr4的显著上调.
- 在YAP-KO心脏中,MEF2结合部位被上调转录丰富,MEF2C蛋白增加.
- MEF2C siRNA 转染减少了 siYAP 在孤立心肌细胞中对基因表达的增强.
结论:
- 心肌细胞YAP激活抑制炎症,部分通过抑制MEF2调节基因.
- YAP在限制心肌细胞炎症反应和维持心脏平衡方面发挥着至关重要的作用.
- 针对YAP-MEF2通路可能为炎症性心脏病提供治疗策略.
关键词:
这就是Mef2的意义.哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈血管新生素是一种这是心肌细胞 (cardiomyocyte).这是一种炎症炎症炎症炎症.更多相关视频
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