Hippo信号通路与肝脏稳态调控及疾病发生

doi:10.16288/j.yczz.17-064

遗传 ›› 2017, Vol. 39 ›› Issue (7): 607-616.doi: 10.16288/j.yczz.17-064

Hippo信号通路与肝脏稳态调控及疾病发生

李玉席(),李俊宏,周大旺()

厦门大学生命科学学院,细胞信号网络协同创新中心,厦门 361102

收稿日期:2017-02-26 修回日期:2017-05-05 出版日期:2017-07-20 发布日期:2017-05-31
作者简介:李玉席,博士研究生,研究方向：细胞生物学。E-mail: liyuxi0608@foxmail.com|周大旺,教授,博士生导师,研究方向：细胞生物学。E-mail: dwzhou@xmu.edu.cn
基金资助:
国家自然科学基金项目(31625010,U1505224,J1310027)

Hippo signaling pathway in liver tissue homeostasis

Yuxi Li(),Junhong Li,Dawang Zhou(),

Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China

Received:2017-02-26 Revised:2017-05-05 Online:2017-07-20 Published:2017-05-31
Supported by:
the National Natural Science Foundation of China(31625010,U1505224,J1310027)

摘要/Abstract

摘要：

肝脏是人体最重要的器官之一,乙肝等病毒性与酒精等非病毒性因素诱发的肝损伤引起肝脏功能衰竭、再生重塑障碍、肝癌等疾病是我国重大社会健康问题,因此,研究肝脏稳态的调控机制对肝病的预防和临床治疗至关重要。Hippo信号通路参与了哺乳动物多种细胞和器官的稳态调控。最近研究表明,Hippo信号通路在肝脏发育、肝细胞命运决定、肝脏再生和癌症发生发展等过程中都发挥了非常重要的作用。因此,Hippo信号通路可成为肝脏相关疾病的治疗提供了新的靶点。本文综述了Hippo信号通路与肝脏稳态调控的相关研究及最新进展,以期为研究肝脏发育和肝脏相关疾病的治疗提供新的思路和策略。

关键词: Hippo/Yap, 肝脏发育, 肝癌, 肝再生

Abstract:

Liver cancer and diseases have become the leading cause of deaths in China. Liver diseases including liver failure and liver cancer can be genetic or caused by a variety of factors that damage the liver, such as viruses and alcohol overdose. However, the underlying mechanisms that maintain liver homeostasis remain unclear. Recent studies show that the Hippo signaling pathway plays a critical role in maintaining liver tissue homeostasis. Dysregulation of the Hippo signaling pathway impairs liver regeneration and remarkly enhances liver overgrowth and tumorigenesis. In this review, we summarize recent progresses on the roles and regulation mechanisms of the Hippo signaling pathway in liver development and diseases.

Key words: Hippo/Yap, liver development, liver cancer, liver regeneration

李玉席, 李俊宏, 周大旺. Hippo信号通路与肝脏稳态调控及疾病发生[J]. 遗传, 2017, 39(7): 607-616.

Yuxi Li, Junhong Li, Dawang Zhou, . Hippo signaling pathway in liver tissue homeostasis[J]. Hereditas(Beijing), 2017, 39(7): 607-616.

参考文献

[1]	Zhou DW, Zhang YY, Wu HT, Barry E, Yin Y, Lawrence E, Dawson D, Willis JE, Markowitz SD, Camargo FD, Avruch J. Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc Natl Acad Sci USA, 2011, 108(49): E1312-E1320.
[2]	Zhou Q, Li L, Zhao B, Guan KL. The hippo pathway in heart development, regeneration, and diseases. Circ Res, 2015, 116(8): 1431-1447.
[3]	Zhou DW, Medoff BD, Chen LF, Li LQ, Zhang XF, Praskova M, Liu M, Landry A, Blumberg RS, Boussiotis VA, Xavier R, Avruch J. The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of na?ve T cells. Proc Natl Acad Sci USA, 2008, 105(51): 20321-20326.
[4]	Geng J, Sun XF, Wang P, Zhang SH, Wang XZ, Wu HT, Hong LX, Xie CC, Li X, Zhao H, Liu QX, Jiang MT, Chen QH, Zhang JJ, Li Y, Song SY, Wang HR, Zhou RB, Johnson RL, Chien KY, Lin SC, Han JH, Avruch J, Chen LF, Zhou DW. Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity. Nat Immunol, 2015, 16(11): 1142-1152.
[5]	Yu FX, Guan KL. The Hippo pathway: regulators and regulations. Genes Dev, 2013, 27(4): 355-371.
[6]	Huang JB, Wu SA, Barrera J, Matthews K, Pan DJ. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. Cell, 2005, 122(3): 421-434.
[7]	Wu SA, Huang JB, Dong JC, Pan DJ. hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. Cell, 2003, 114(4): 445-456.
[8]	Chan EHY, Nousiainen M, Chalamalasetty RB, Sch?fer A, Nigg EA, Silljé HHW. The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene, 2005, 24(12): 2076-2086.
[9]	Yin F, Yu JZ, Zheng YG, Chen Q, Zhang NL, Pan DJ. Spatial organization of Hippo signaling at the plasma membrane mediated by the tumor suppressor Merlin/NF2. Cell, 2013, 154(6): 1342-1355.
[10]	Hamaratoglu F, Willecke M, Kango-Singh M, Nolo R, Hyun E, Tao C, Jafar-Nejad H, Halder G. The tumour- suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nat Cell Biol, 2006, 8(1): 27-36.
[11]	Bennett FC, Harvey KF. Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway. Curr Biol, 2006, 16(21): 2101-2110.
[12]	Greenbaum LE. The ductal plate: a source of progenitors and hepatocytes in the adult liver. Gastroenterology, 2011, 141(4): 1152-1155.
[13]	Zhang NL, Bai HB, David KK, Dong JX, Zheng YG, Cai J, Giovannini M, Liu PT, Anders RA, Pan DJ. The Merlin/NF2 tumor suppressor functions th

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

Hippo信号通路与肝脏稳态调控及疾病发生

Hippo signaling pathway in liver tissue homeostasis

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics