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首页> 外文期刊>Proteome science >The hepatocyte proteome in organotypic rat liver models and the influence of the local microenvironment
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The hepatocyte proteome in organotypic rat liver models and the influence of the local microenvironment

机译：器官型大鼠肝模型的肝细胞蛋白质组及其局部微环境的影响。

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BackgroundLiver models that closely mimic the in vivo microenvironment are useful for understanding liver functions, capabilities, and intercellular communication processes. Three-dimensional (3D) liver models assembled using hepatocytes and liver sinusoidal endothelial cells (LSECs) separated by a polyelectrolyte multilayer (PEM) provide a functional system while also permitting isolation of individual cell types for proteomic analyses. MethodsTo better understand the mechanisms and processes that underlie liver model function, hepatocytes were maintained as monolayers and 3D PEM-based formats in the presence or absence of primary LSECs. The resulting hepatocyte proteomes, the proteins in the PEM, and extracellular levels of urea, albumin and glucose after three days of culture were compared. ResultsAll systems were ketogenic and found to release glucose. The presence of the PEM led to increases in proteins associated with both mitochondrial and peroxisomal-based β-oxidation. The PEMs also limited production of structural and migratory proteins associated with dedifferentiation. The presence of LSECs increased levels of Phase I and Phase II biotransformation enzymes as well as several proteins associated with the endoplasmic reticulum and extracellular matrix remodeling. The proteomic analysis of the PEMs indicated that there was no significant change after three days of culture. These results are discussed in relation to liver model function. ConclusionsHeterotypic cell-cell and cell-ECM interactions exert different effects on hepatocyte functions and phenotypes.
机译：紧密模仿体内微环境的BackgroundLiver模型可用于了解肝脏功能，功能和细胞间通讯过程。使用由聚电解质多层（PEM）分隔的肝细胞和肝窦形内皮细胞（LSEC）组装的三维（3D）肝模型提供了功能系统，同时还允许分离单个细胞类型以进行蛋白质组学分析。方法为了更好地了解构成肝模型功能的机制和过程，在存在或不存在原发性LSEC的情况下，肝细胞均以单层和基于3D PEM的形式进行维护。比较培养三天后得到的肝细胞蛋白质组，PEM中的蛋白质以及尿素，白蛋白和葡萄糖的细胞外水平。结果所有系统都是生酮的，并发现释放葡萄糖。 PEM的存在导致与线粒体和基于过氧化物酶体的β-氧化相关的蛋白质增加。 PEM还限制了与去分化相关的结构蛋白和迁移蛋白的生产。 LSEC的存在增加了I相和II相生物转化酶以及与内质网和细胞外基质重塑相关的几种蛋白质的水平。对PEM的蛋白质组学分析表明，培养三天后无明显变化。这些结果与肝功能模型有关。结论异型细胞-细胞和细胞-ECM的相互作用对肝细胞功能和表型的影响不同。

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