Enhanced liver regeneration following changes induced by hepatocyte-specific genetic ablation of integrin-linked kinase.
Enhanced liver regeneration following changes induced by hepatocyte-specific genetic ablation of integrin-linked kinase.
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DOI：
10.1002/hep.23059
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发表时间：
2009-09
期刊：
影响因子：
13.5
通讯作者：
Michalopoulos, George K.
中科院分区：
文献类型：
--
作者：
Apte, Udayan;Gkretsi, Vasiliki;Bowen, William C.;Mars, Wendy M.;Luo, Jian-Hua;Donthamsetty, Shashikiran;Orr, Ann;Monga, Satdarshan P. S.;Wu, Chuanyue;Michalopoulos, George K.
部分肝切除术后肝再生后，肝脏精确地生长回其原始质量，并且不超过它。调节这种“肝稳定”的机制尚不清楚，迄今为止没有发现例外。虽然启动肝再生的途径已被充分研究，但涉及肝再生终止的机制尚不清楚。在这里，我们报告了整合素连接激酶（ILK）（通过整合素受体参与细胞外基质（ECM）信号传导）和/或ILK肝细胞靶向清除后随之发生的肝适应，对于正确终止肝再生至关重要。在部分肝切除术（PHX）后，具有肝脏特异性ILK消融（ILK-KO-Liver）的小鼠表现出终止缺陷，导致肝脏比其原始PHX前质量大58%。PHX后肝脏质量的这种增加是由于持续的细胞增殖，部分是由通过HGF/Met和β-连环蛋白途径和Hippo激酶途径的信号传导增加驱动的。数据表明，通过ILK介导的ECM信号对于正确终止肝脏再生至关重要。这是第一个证据的缺陷，导致受损终止再生和过度积累的肝脏重量后，部分肝切除术。
Following liver regeneration after partial hepatectomy, liver grows back precisely to its original mass and does not exceed it. The mechanism regulating this “hepatostat” is not clear and no exceptions have been found to date. While pathways initiating liver regeneration have been well studied, mechanisms involved in termination of liver regeneration are unclear. Here we report that Integrin Linked Kinase (ILK) (involved in transmission of the extracellular matrix (ECM) signaling via integrin receptors) and/or hepatic adaptations that ensue following ILK hepatocyte-targeted removal, are critical for proper termination of liver regeneration. Following partial hepatectomy (PHX), mice with a liver-specific ILK ablation (ILK-KO-Liver) demonstrate a termination defect resulting in 58% larger liver than their original pre-PHX mass. This increase in post-PHX liver mass is due to sustained cell proliferation driven in part by increased signaling through HGF/Met, and β-catenin pathway and Hippo Kinase pathways. The data indicate that ECM-mediated signaling via ILK is essential in proper termination of liver regeneration. This is the first evidence of a defect leading to impaired termination of regeneration and excessive accumulation of liver weight following partial hepatectomy.
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影响因子：
13.5
作者：
Gkretsi, Vasiliki;Apte, Udayan;Mars, Wendy M.;Bowen, William C.;Luo, Jian-Hua;Yang, Yu;Yu, Yan P.;Orr, Ann;St-Arnaud, Rene;Dedhar, Shoukat;Kaestner, Klaus H.;Wu, Chuanyue;Michalopoulos, George K.
通讯作者：
Michalopoulos, George K.
影响因子：
15.9
作者：
BISSELL, DM;ARENSON, DM;ROLL, FJ
通讯作者：
ROLL, FJ
影响因子：
13.5
作者：
Oe, S;Lemmer, ER;Thorgeirsson, SS
通讯作者：
Thorgeirsson, SS
影响因子：
13.5
作者：
Fausto, N;Campbell, JS;Riehle, KJ
通讯作者：
Riehle, KJ
影响因子：
13.5
作者：
Gkretsi, Vasiliki;Mars, Wendy M.;Michalopoulos, George K.
通讯作者：
Michalopoulos, George K.