心脏纤维细胞特异激活转录因子3通过抑制MAP2K3-p38信号来保护心脏衰竭
Yulin Li1, Zhenya Li1, Congcong Zhang1
1From Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, China (Y.L., Z.L., C.Z., P.L., Y.W., C.W., J.D.); and Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., X.-L.M.).
Circulation
|March 3, 2017
概括
激活转录因子3 (ATF3) 通过抑制Map2K3和p38信号来保护心脏免受高血压重塑. 在心脏纤维细胞中提升ATF3可能为心力衰竭提供一种新疗法.
科学领域:
- 心血管生物学
- 疾病的分子机制
- 心脏纤维化和缩
背景情况:
- 高血压心室重塑是导致心力衰竭的主要原因.
- 这一过程的分子路径尚未完全理解.
研究的目的:
- 研究激活转录因子3 (ATF3) 在高血压心脏重塑中的作用.
- 阐明ATF3影响心室重塑的分子机制.
主要方法:
- 使用一种以发现为导向的方法来识别高血压心脏中的ATF3.
- 在心脏纤维细胞中使用功能丧失 (ATF3淘汰) 和功能增加 (转基因过度表达) 研究.
- 进行了转录组和ChIP测序,以及体外和体内实验.
主要成果:
- 在高血压和高性心脏中,ATF3表达升高.
- 而过度表达则改善了这种情况.
- 通过招募HDAC1,ATF3直接抑制了Map2K3的表达,抑制了下游的p38信号传递和益纤维化通路.
结论:
- 心脏纤维细胞的ATF3上调可以防止高血压重塑.
- 这种保护通过抑制Map2K3和随后的p38转化生长因子-β信号发生.
- 针对心脏纤维细胞ATF3是高血压心脏病的潜在治疗策略.
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