Hippo pathway coactivators Yap and Taz are required to coordinate mammalian liver regeneration.
Hippo pathway coactivators Yap and Taz are required to coordinate mammalian liver regeneration.
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DOI：
10.1038/emm.2017.205
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发表时间：
2018-01-05
影响因子：
12.8
通讯作者：
Johnson RL
中科院分区：
文献类型：
--
作者：
Lu L;Finegold MJ;Johnson RL
哺乳动物的肝脏在损伤后具有显著的修复能力。切除多达三分之二的肝脏质量会导致一系列事件，包括细胞外基质重塑、协调的肝细胞周期重新进入、肝脏质量的恢复和组织重建，以使受损的肝脏恢复到其正常状态。虽然我们对哺乳动物肝脏的再生能力的认识已经有了相当大的进步，但仍然存在许多悬而未决的问题，例如：当适当的质量恢复时，再生肝脏如何停止增殖，以及这些机制与发育过程中器官大小的正常调节有何关系？河马途径被认为在调节这两个事件中起中心作用：发育过程中器官大小的控制和随后的再生。在这份报告中，我们研究了河马途径的关键成分YAP和Taz在肝脏器官大小调节中的作用，在发育和内稳态的背景下都是如此。我们的研究表明，与目前的范例相反，YAP/Taz不是肝脏大小发育调节所必需的，而是肝脏正常再生所必需的。在缺乏YAP和TAZ的肝脏中，新生儿和成年人的肝脏质量增加。然而，YAP/Taz耗尽的肝脏在肝脏再生方面表现出严重的缺陷，包括无法恢复肝脏质量和正确协调细胞周期进入。综上所述，我们的结果强调了在肝脏再生过程中对河马途径的需求，并表明在发育期间和成人中，还有其他途径与河马信号合作来控制肝脏大小。
The mammalian liver has a remarkable capacity for repair following injury. Removal of up to two-third of liver mass results in a series of events that include extracellular matrix remodeling, coordinated hepatic cell cycle re-entry, restoration of liver mass and tissue remodeling to return the damaged liver to its normal state. Although there has been considerable advancement of our knowledge concerning the regenerative capacity of the mammalian liver, many outstanding questions remaining, such as: how does the regenerating liver stop proliferating when appropriate mass is restored and how do these mechanisms relate to normal regulation of organ size during development? Hippo pathway has been proposed to be central in mediating both events: organ size control during development and following regeneration. In this report, we examined the role of Yap and Taz, key components of the Hippo pathway in liver organ size regulation, both in the context of development and homeostasis. Our studies reveal that contrary to the current paradigms that Yap/Taz are not required for developmental regulation of liver size but are required for proper liver regeneration. In livers depleted of Yap and Taz, liver mass is elevated in neonates and adults. However, Yap/Taz-depleted livers exhibit profound defects in liver regeneration, including an inability to restore liver mass and to properly coordinate cell cycle entry. Taken together, our results highlight requirements for the Hippo pathway during liver regeneration and indicate that there are additional pathways that cooperate with Hippo signaling to control liver size during development and in the adult.
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影响因子：
10.5
作者：
Meng Z;Moroishi T;Guan KL
通讯作者：
Guan KL
DOI：
10.1126/science.1199010
发表时间：
2011-04-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Heallen T;Zhang M;Wang J;Bonilla-Claudio M;Klysik E;Johnson RL;Martin JF
通讯作者：
Martin JF
影响因子：
7.2
作者：
Penzo-Mendez, Alfredo I.;Stanger, Ben Z.
通讯作者：
Stanger, Ben Z.
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia
影响因子：
13.5
作者：
Bai, Haibo;Zhang, Nailing;Xu, Yang;Chen, Qian;Khan, Mehtab;Potter, James J.;Nayar, Suresh K.;Cornish, Toby;Alpini, Gianfranco;Bronk, Steven;Pan, Duojia;Anders, Robert A.
通讯作者：
Anders, Robert A.