Hepatocyte growth factor accelerates the proliferation of hepatic oval cells and possibly promotes the differentiation in a 2-acetylaminofluorene/partial hepatectomy model in rats
Hepatocyte growth factor accelerates the proliferation of hepatic oval cells and possibly promotes the differentiation in a 2-acetylaminofluorene/partial hepatectomy model in rats
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DOI：
10.1111/j.1440-1746.2005.03922.x
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发表时间：
2005-11-01
影响因子：
4.1
通讯作者：
Tsubouchi, H
中科院分区：
文献类型：
--
作者：
Hasuike, S;Ido, A;Tsubouchi, H
背景：肝细胞生长因子（HGF）是促进成熟肝细胞增殖的主要药物。本文采用2-乙酰氨基芴/部分肝切除（2-AAF/PH）模型，探讨HGF对大鼠肝卵圆细胞增殖和分化的影响。方法：重组人HGF （0.2 mg/d）通过渗透泵腹腔植入2-AAF/PH大鼠，并联合肝切除术（第0天）。结果：在第8天，HGF显著增大了门静脉周围卵圆形细胞的嗜碱性区。在对照动物中，肝脏中甲胎蛋白（AFP）的表达逐渐上调，在第12天显著升高。在hgf处理的大鼠中，AFP的表达在较早的日期受到刺激，并在第12天降至不可检测的水平。相反，即使在HGF停止给药后，白蛋白转录本的表达也继续增加，在第12天达到极高的水平。此外，用HGF治疗还可以早期刺激肝细胞核因子-1 α和-4 α的表达。结论：这些结果表明，除了肝卵圆细胞的增殖外，HGF在体内还可能促进肝细胞向肝细胞的分化，提示重组人HGF加速了严重损伤肝脏的再生，使成熟肝细胞的增殖受到损害。(C) 2005 Blackwell出版亚洲有限公司
Background: Hepatocyte growth factor (HGF) is the primary agent promoting the proliferation of mature hepatocytes. The purpose of the present paper was to clarify the effects of HGF on the proliferation and differentiation of hepatic oval cells using a 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH) model in rats.Methods: Recombinant human HGF (0.2 mg/day) was administered to 2-AAF/PH rats for 7 days using osmotic pumps intraperitoneally implanted in conjunction with hepatectomy (day zero).Results: Periportal basophilic areas consisting of oval cells were significantly enlarged by treatment with HGF on day 8. In control animals, expression of alpha-fetoprotein (AFP) in the liver was gradually upregulated, leading a marked increase on day 12. In HGF-treated rats, AFP expression was stimulated at an earlier date and decreased to an undetectable level on day 12. Conversely, expression of albumin transcripts, which was stimulated by HGF-treatment at a later date, continued to increase even after HGF administration ceased, leading to an extremely high level on day 12. Moreover, treatment with HGF also stimulated the expression of hepatocyte nuclear factor-1 alpha and -4 alpha at an early date.Conclusions: These results indicate that, besides the proliferation of hepatic oval cells, HGF possibly promotes the differentiation to hepatocytes in vivo, suggesting that recombinant human HGF accelerates the regeneration of severely damaged livers, a situation in which the proliferation of mature hepatocytes is impaired. (C) 2005 Blackwell Publishing Asia Pty Ltd.