Compensatory recovery of liver mass by Akt-mediated hepatocellular hypertrophy in liver-specific STAT3-deficient mice
Compensatory recovery of liver mass by Akt-mediated hepatocellular hypertrophy in liver-specific STAT3-deficient mice
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DOI：
10.1016/j.jhep.2005.03.027
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发表时间：
2005-11-01
影响因子：
25.7
通讯作者：
Ozaki, M
中科院分区：
文献类型：
--
作者：
Haga, S;Ogawa, W;Ozaki, M
背景/目的：肝切除术后的肝再生是复杂的，涉及多种相互作用的因素。本研究旨在研究肝细胞增殖和肥大在肝切除术后肝再生中的作用，肝特异性STAT 3基因敲除（LS 3-KO）小鼠缺乏促有丝分裂活性。结果：LS 3-KO小鼠PH后肝细胞增殖明显受到抑制，cyclinD 1转录水平降低，细胞凋亡率降低，细胞凋亡率降低。然而，LS 3-KO小鼠PH后肝脏质量充分恢复，几乎等于对照小鼠。肝细胞生长的分析显示，肝切除术后的细胞大小在LS 3-KO小鼠中显著大于对照小鼠。肝切除术在LS 3-KO小鼠中诱导Akt、p70（S6 K）、mTOR和GSK-3 β的立即但短暂的磷酸化，比在对照小鼠中多得多。此外，腺病毒转染显性失活突变体的Akt控制和LS 3-KO小鼠导致肝再生不足hepatectics.Conclusions：PI 3-K/Akt介导的响应性肝细胞肥大可能是必不可少的肝切除术后的肝再生和充分补偿肝再生，即使在STAT 3缺陷的肝脏，其中细胞增殖受损。(c)2005年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Liver regeneration following hepatectomy is complicated and involves a variety of interacting factors. The present study was designed to study the roles of proliferation and hypertrophy of hepatocytes in liver regeneration following hepatectomy in liver-specific STAT3-knockout (LS3-KO) mice lacking mitogenic activity.Methods: Partial hepatectomy was performed in LS3-KO and control mice. Liver regeneration was estimated by the liver weight, cell proliferation and cell size, and the related cellular signals were analyzed.Results: Proliferation of hepatocytes following PH was markedly suppressed in LS3-KO mice with reduced cyclinD1 transcript. However, liver mass recovered sufficiently following PH in LS3-KO mice almost equal to that of control mice. Analysis of hepatocellular growth revealed that cell size following hepatectomy was significantly larger in LS3-KO mice than in control mice. Hepatectomy induced immediate but transient phosphorylation of Akt, p70(S6K), mTOR and GSK-3 beta in LS3-KO mice much more than in control mice. Additionally, adenoviral transfection of dominant negative mutant of Akt to control and LS3-KO mice led to insufficient liver regeneration following hepatectomy.Conclusions: PI3-K/Akt-mediated responsive hepatocellular hypertrophy may be essential for liver regeneration following hepatectomy and sufficiently compensated liver regeneration even in STAT3-deficient liver, in which cell proliferation is impaired. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.