Gene expression profiles in liver regeneration with oval cell induction

Gene expression profiles in liver regeneration with oval cell induction
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DOI:
10.1016/j.bbrc.2004.03.057
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发表时间:
2004-04-30
影响因子:
3.1
通讯作者:
Seki, N
Seki, N
中科院分区:
生物学4区
文献类型:
--
作者:
Arai, M;Yokosuka, O;Seki, N

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肝脏具有独特的再生能力,即使在成年期也是如此。虽然成熟肝细胞可以自己增殖,但干细胞在肝再生中也起着关键作用,卵圆细胞被认为是活化的肝干细胞的后代。在此,我们研究了基因表达谱的条件下诱导卵圆细胞,使用微阵列分析。采用两种方法诱导卵圆细胞。在第一组中,动物接受了含N-2-乙酰氨基芴(AAF)的饮食和部分肝切除术(PHx)的联合治疗。在第二组中,向动物提供含胆碱缺乏和正常饲料1:1混合物的饲料,以及含0.075%乙醇的饮用水。使用内部cDNA微阵列组成的2304 cDNA克隆从小鼠肝脏,69和89个基因,分别被发现在这两个模型中上调。六个基因,即,胰岛素样生长因子结合蛋白-1、CYP 4a 14、肉毒碱辛酰转移酶、骨桥蛋白和两个表达序列标签(EST)在这些模型中表达上调,而在单纯PHx的普通模型中未表达。它们可能在卵圆细胞的诱导中被特异性激活,并有助于澄清肝再生过程中发生的干细胞刺激的性质。(C)2004年爱思唯尔公司All rights reserved.
The liver has the unique ability to regenerate even in adulthood. While mature hepatocytes can proliferate by themselves, stem cells also play a critical role in liver regeneration and oval cells are considered to be the progeny of activated hepatic stem cells. We herein investigated the gene expression profiles in the conditions inducing oval cells, using microarray analysis. Two approaches were used to induce oval cells. In the first, animals were treated with a combination of an N-2-acetylaminofluorene (AAF)-containing diet and partial hepatectomy (PHx). In the second, animals were supplied with chow containing a 1:1 mixture of choline-deficient and normal diets, as well as 0.075% ethionine in drinking water. Using in-house cDNA microarrays consisting of 2304 cDNA clones from the mouse liver, 69 and 89 genes, respectively, were found to be up-regulated in these two models. Six genes, i.e., those for insulin-like growth factor binding protein-1, CYP4a14, carnitine octanoyltransferase, osteopontin, and two expressed sequence tags (ESTs) were up-regulated in these models but not in ordinary model with PHx alone. They might be specifically activated in the induction of oval cells, and help to clarify the nature of stem cell stimulation that occurs during liver regeneration. (C) 2004 Elsevier Inc. All rights reserved.