3D cultured immortalized human hepatocytes useful to develop drugs for blood-borne HCV
3D cultured immortalized human hepatocytes useful to develop drugs for blood-borne HCV
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DOI：
10.1016/j.bbrc.2008.12.054
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发表时间：
2009-02-06
影响因子：
3.1
通讯作者：
Hijikata, Makoto
中科院分区：
文献类型：
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作者：
Aly, Hussein Hassan;Shimotohno, Kunitada;Hijikata, Makoto
由于天然丙型肝炎病毒（HCV）变异的高多态性，现有的重组丙型肝炎病毒复制模型无法有效地开发有效的抗丙型肝炎病毒药物。在目前的研究中，我们描述了一个体外系统，该系统使用在三维（3D）培养系统中培养的永生化原代人肝细胞系，支持从患者血液中感染和复制天然HCV。将3D系统中培养的细胞与现有2D系统中培养的细胞的基因表达谱进行比较，发现过氧化物酶体增殖因子激活受体α (PPAR α)信号激活的几个基因上调。此外，使用PPAR α激动剂和拮抗剂，我们还分析了PPAR α信号在该系统中对HCV复制的调节作用。本研究中描述的3D体外系统为寻找针对各种HCV株的新型抗HCV策略提供了重要的见解。(c) 2008爱思唯尔公司版权所有。
Due to the high polymorphism of natural hepatitis C virus (HCV) variants, existing recombinant HCV replication models have failed to be effective in developing effective anti-HCV agents. In the current study, we describe an in vitro system that Supports the infection and replication of natural HCV from patient blood using an immortalized primary human hepatocyte cell line cultured in a three-dimensional (3D) culture system. Comparison of the gene expression profile of cells cultured in the 3D system to those cultured in the existing 2D system demonstrated an up-regulation of several genes activated by peroxisome proliferator-activated receptor alpha (PPAR alpha) signaling. Furthermore, using PPAR alpha agonists and antagonists, we also analyzed the effect of PPAR alpha signaling on the modulation of HCV replication using this system. The 3D in vitro system described in this study provides significant insight into the search for novel anti-HCV strategies that are specific to various strains of HCV. (c) 2008 Elsevier Inc. All rights reserved.