Hippo信号通路与心血管发育及疾病调控

doi:10.16288/j.yczz.17-039

遗传 ›› 2017, Vol. 39 ›› Issue (7): 576-587.doi: 10.16288/j.yczz.17-039

Hippo信号通路与心血管发育及疾病调控

王永煜¹(),余薇²,周斌²()

1. 温州医科大学基础医学院,温州 325035
2. 中国科学院上海生命科学研究院生物化学与细胞生物学研究所,细胞生物学国家重点实验室,上海 200031

收稿日期:2017-02-09 修回日期:2017-03-07 出版日期:2017-07-20 发布日期:2017-05-23
作者简介:王永煜，博士，研究员，研究方向：干细胞与心血管再生。E-mail：yywangut@163.com|周斌，博士，研究员，研究方向：心血管发育与再生。E-mail：zhoubin@sibs.ac.cn
基金资助:
国家自然科学基金项目(编号：81670454,81270321,31625019,91639302)资助[Supported by the National Natural Science Foundation of China (Nos. 81670454, 81270321, 31625019, 91639302)]

Hippo signaling pathway in cardiovascular development and diseases

Yongyu Wang¹(),Wei Yu²,Bin Zhou²()

1. College of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China
2. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

Received:2017-02-09 Revised:2017-03-07 Online:2017-07-20 Published:2017-05-23

摘要/Abstract

摘要：

心血管疾病已成为中国乃至全球首位死亡原因,探索心血管系统发育及调控异常的原因及相关机制可以为心血管疾病的预防和治疗提供重要的科学依据。Hippo信号通路是新近发现的在调节器官大小、细胞增殖及凋亡、干细胞命运等方面具有重要功能的一条信号通路。Hippo信号通路的不同成分参与心脏血管的发育和心血管细胞增殖、分化等功能调控,影响损伤后修复及再生等过程,该通路调节异常可引起心血管疾病,如心梗、心肌肥大、血管内膜增生、动脉硬化等。本文综述了Hippo信号通路对心血管系统发育和疾病调控的相关研究及最新进展,以期为Hippo通路在心血管疾病的发病机制及临床转化研究提供潜在的理论基础。

关键词: Hippo/YAP, 心脏发育, 心肌再生, 心血管疾病, 动脉硬化

Abstract:

Cardiovascular diseases have become the leading cause of death in the world. Understanding the development of cardiovascular system and the pathogenesis of cardiovascular diseases will promote the generation of novel preventive and therapeutic strategy. The Hippo pathway is a recently identified signaling cascade that plays a critical role in organ size control, cell proliferation, apoptosis and fate determination of stem cells. Gene knockout and transgenic mouse models have revealed that the Hippo signaling pathway is involved in heart development, cardiomyocyte proliferation, apoptosis, hypertrophy and cardiac regeneration. The Hippo signaling pathway also regulates vascular development, differentiation and various functions of vascular cells. Dysregulation of the Hippo signaling pathway leads to different kinds of cardiovascular diseases, such as myocardial infarction, cardiac hypertrophy, neointima formation and atherosclerosis. In this review, we briefly summarize current research on the roles and regulation mechanisms of the Hippo signaling pathway in cardiovascular development and diseases.

Key words: Hippo/YAP, heart development, cardiac regeneration, cardiovascular diseases, atherosclerosis

王永煜,余薇,周斌. Hippo信号通路与心血管发育及疾病调控[J]. 遗传, 2017, 39(7): 576-587.

Yongyu Wang,Wei Yu,Bin Zhou. Hippo signaling pathway in cardiovascular development and diseases[J]. Hereditas(Beijing), 2017, 39(7): 576-587.

参考文献

[1]	Zhou Q, Li L, Zhao B, Guan KL. The hippo pathway in heart development, regeneration, and diseases. Circ Res, 2015, 116(8): 1431-1447.
[2]	Yu FX, Zhao B, Guan KL. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell, 2015, 163(4): 811-828.
[3]	McPherson JP, Tamblyn L, Elia A, Migon E, Shehabeldin A, Matysiak-Zablocki E, Lemmers B, Salmena L, Hakem A, Fish J, Kassam F, Squire J, Bruneau BG, Hande MP, Hakem R. Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity. EMBO J, 2004, 23(18): 3677-3688.
[4]	Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E, Johnson RL, Martin JF. Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science, 2011, 332(6028): 458-461.
[5]	Song H, Mak KK, Topol L, Yun KS, Hu J, Garrett L, Chen YB, Park O, Chang J, Simpson RM, Wang CY, Gao B, Jiang J, Yang YZ. Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proc Natl Acad Sci USA, 2010, 107(4): 1431-1436.
[6]	Matsui Y, Nakano N, Shao D, Gao SM, Luo WT, Hong C, Zhai PY, Holle E, Yu XZ, Yabuta N, Tao WF, Wagner T, Nojima H, Sadoshima J. Lats2 is a negative regulator of myocyte size in the heart. Circ Res, 2008, 103(11): 1309-1318.
[7]	Morin-Kensicki EM, Boone BN, Howell M, Stonebraker JR, Teed J, Alb JG, Magnuson TR, O'Neal W, Milgram SL. Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted disruption of Yap65. Mol Cell Biol, 2006, 26(1): 77-87.
[8]	Xin M, Kim Y, Sutherland LB, Murakami M, Qi XX, McAnally J, Porrello ER, Mahmoud AI, Tan W, Shelton JM, Richardson JA, Sadek HA, Bassel-Duby R, Olson EN. Hippo pathway effector Yap promotes cardiac regeneration. Proc Natl Acad Sci USA, 2013, 110(34): 13839-13844.
[9]	Xin M, Kim Y, Sutherland LB, Qi XX, McAnally J, Schwartz RJ, Richardson JA, Bassel-Duby R, Olson EN. Regulation of insulin-like growth factor signaling by Yap governs cardiomyocyte proliferation and embryonic heart size. Sci Signal, 2011, 4(196): ra70
[10]	von Gise A, Lin ZQ, Schlegelmilch K, Honor LB, Pan GM, Buck JN, Ma Q, Ishiwata T, Zhou B, Camargo FD, Pu WT. YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. Proc Natl Acad Sci USA, 2012, 109(7): 2394-2399.
[11]	Miesfeld JB, Link BA. Establishment of transgenic lines to monitor and manipulate Yap/Taz-Tead activity in zebrafish reveals both evolutionarily conserved and divergent functions of the Hippo pathway. Mech Dev, 2014, 133: 177-188.
[12]	Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, Zhao JG, Yuan HX, Tumaneng K, Li HR, Fu XD, Mills GB, Guan KL. Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell, 2012, 150(4): 78

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Hippo信号通路与心血管发育及疾病调控

Hippo signaling pathway in cardiovascular development and diseases

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