The hippo pathway in heart development, regeneration, and diseases.
The hippo pathway in heart development, regeneration, and diseases.
复制标题
心脏发育、再生和疾病中的河马通路。
DOI：
10.1161/circresaha.116.303311
复制
发表时间：
2015-04-10
影响因子：
20.1
通讯作者：
Guan KL
中科院分区：
文献类型：
--
作者：
Zhou Q;Li L;Zhao B;Guan KL
心脏是哺乳动物发育过程中形成的第一个器官。一颗大小合适、功能正常的心脏在整个生命过程中至关重要。由于损伤或疾病导致的心肌细胞丢失会导致心力衰竭，这是人类发病率和死亡率的主要原因。不幸的是，成人心脏的再生潜力是有限的。河马途径是新近发现的一种信号级联反应，通过抑制细胞增殖、促进细胞凋亡、调节干细胞/祖细胞的命运，以及在某些情况下限制细胞大小，在进化上起到保守的作用。有趣的是，研究表明，这一途径在调节心肌细胞增殖和心脏大小方面起着关键作用。河马途径的失活或其下游效应器的激活，是与Yes相关的蛋白转录共激活因子，可以促进心脏再生。已知的河马信号通路的几个上游信号，如机械应激、G蛋白偶联受体信号和氧化应激，在心脏生理学中起着关键作用。此外，YES相关蛋白已被证明通过多种转录机制调节心肌细胞的命运。在这篇综述中，我们总结和讨论了河马通路在心脏发育、损伤和再生中的作用和机制的最新研究结果。
The heart is the first organ formed during mammalian development. A properly sized and functional heart is vital throughout the entire lifespan. Loss of cardiomyocytes because of injury or diseases leads to heart failure, which is a major cause of human morbidity and mortality. Unfortunately, regenerative potential of the adult heart is limited. The Hippo pathway is a recently identified signaling cascade that plays an evolutionarily conserved role in organ size control by inhibiting cell proliferation, promoting apoptosis, regulating fates of stem/progenitor cells, and in some circumstances, limiting cell size. Interestingly, research indicates a key role of this pathway in regulation of cardiomyocyte proliferation and heart size. Inactivation of the Hippo pathway or activation of its downstream effector, the Yes-associated protein transcription coactivator, improves cardiac regeneration. Several known upstream signals of the Hippo pathway such as mechanical stress, G-protein-coupled receptor signaling, and oxidative stress are known to play critical roles in cardiac physiology. In addition, Yes-associated protein has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms. In this review, we summarize and discuss current findings on the roles and mechanisms of the Hippo pathway in heart development, injury, and regeneration.