BAG3定位在心脏纤维细胞中的线粒体中,并调节线粒细胞衰变
Thomas G Martin1, Laura A Sherer1, Jonathan A Kirk1
1Department of Cell and Molecular Physiology, Loyola University Stritch School of Medicine, Maywood, Illinois, United States.
概括
心脏纤维细胞中的Bcl2关联的乙醇基3 (BAG3) 蛋白质通过支持线粒细胞衰变和预防纤维化,对保持心脏健康至关重要. 降低BAG3水平会通过促进纤维细胞激活和病态重塑来恶化心脏病.
科学领域:
- 心血管生物学 心血管生物学
- 细胞应激反应的应激反应
背景情况:
- 与Bcl2相关的乙醇基因3 (BAG3) 对心脏中的蛋白质质量控制至关重要.
- 降低BAG3表达与心脏功能障碍和扩张性心肌病相关.
- 在心脏纤维细胞中BAG3的作用,是心脏重塑的关键贡献者,仍然在很大程度上是未知的.
研究的目的:
- 为了研究BAG3在初级心脏纤维细胞中的功能.
- 探索BAG3在线粒细胞衰变,纤维细胞激活和纤维细胞重塑中的作用.
- 了解BAG3-Hsp70相互作用对纤维细胞线粒体功能的影响.
主要方法:
- 主要小鼠新生儿心脏纤维细胞被用于研究BAG3的表达和局部化.
- 进行了BAG3淘汰,以评估其对线粒细胞衰变和纤维细胞激活的影响.
- 使用JG-98抑制了BAG3和HSP70之间的相互作用,以评估线粒体形态和自.
主要成果:
- BAG3在心脏纤维细胞中表达,并定位到线粒体.
- 降低BAG3 knockdown减少了线粒,增加了纤维细胞激活,并促进了纤维细胞重塑.
- 抑制BAG3-Hsp70相互作用降低了自,线粒素-2表达,并破坏了线粒体形态学.
结论:
- BAG3促进了线粒并促进了心脏纤维细胞中的纤维细胞静止.
- 降低心力衰竭中的BAG3水平可能会通过sarcomere独立的途径加剧心脏纤维化.
- BAG3在维持心脏纤维细胞平衡和防止病态重塑方面发挥着至关重要的作用.
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