在肝脏特异性STAT3缺陷小鼠中，通过Akt介导的肝细胞肥大实现肝脏质量的代偿性恢复。
Compensatory recovery of liver mass by Akt-mediated hepatocellular hypertrophy in liver-specific STAT3-deficient mice.
作者信息
Haga Sanae, Ogawa Wataru, Inoue Hiroshi, Terui Keita, Ogino Tetsuya, Igarashi Rumi, Takeda Kiyoshi, Akira Shizuo, Enosawa Shin, Furukawa Hiroyuki, Todo Satoru, Ozaki Michitaka
机构信息
Department of Surgery, Hokkaido University Graduate School of Medicine, Faculty of Medicine, Sapporo, Japan.
出版信息
J Hepatol. 2005 Nov;43(5):799-807. doi: 10.1016/j.jhep.2005.03.027. Epub 2005 May 31.
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, p70S6K, mTOR and GSK-3beta 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.
背景/目的：肝切除术后的肝再生过程复杂，涉及多种相互作用的因素。本研究旨在探讨在缺乏促有丝分裂活性的肝脏特异性 STAT3 基因敲除（LS3-KO）小鼠中，肝细胞增殖和肥大在肝切除术后肝再生中的作用。
方法
对 LS3-KO 小鼠和对照小鼠进行部分肝切除术。通过肝脏重量、细胞增殖和细胞大小评估肝再生情况，并分析相关细胞信号。
结果
在 LS3-KO 小鼠中，肝切除术后肝细胞增殖明显受到抑制，细胞周期蛋白 D1 转录本减少。然而，LS3-KO 小鼠肝切除术后肝脏质量仍能充分恢复，几乎与对照小鼠相当。对肝细胞生长的分析显示，肝切除术后 LS3-KO 小鼠的细胞大小明显大于对照小鼠。肝切除术后，LS3-KO 小鼠中 Akt、p70S6K、mTOR 和 GSK-3β 的磷酸化立即出现但短暂，且比对照小鼠更为明显。此外，将 Akt 显性负突变体腺病毒转染至对照小鼠和 LS3-KO 小鼠，导致肝切除术后肝再生不足。
结论
PI3-K/Akt 介导的反应性肝细胞肥大可能对肝切除术后的肝再生至关重要，即使在 STAT3 缺陷的肝脏中，细胞增殖受损时也能充分补偿肝再生。
Zotero 插件