Batusic Danko S, Cimica Velasco, Chen Yonglong, Tron Kyrylo, Hollemann Thomas, Pieler Tomas, Ramadori Giuliano
Department of Internal Medicine, Section of Gastroenterology and Endocrinology, Georg-August-University, Göttingen, 37099, Germany.
Histochem Cell Biol. 2005 Sep;124(3-4):245-60. doi: 10.1007/s00418-005-0021-0. Epub 2005 Oct 28.
Under certain conditions liver regeneration can be accomplished by hepatic progenitor cells ("oval cells"). So far, only few factors have been identified to be uniquely regulated by the "oval cell" compartment. Using macroarray analysis in a rat model of oval cell proliferation (treatment with 2-acetylaminofluorene and partial hepatectomy, AAF + PH), we identified 12 differentially expressed genes compared to appropriate control models (AAF treatment and sham operation or AAF treatment alone). Further analysis in models of normal liver regeneration (ordinary PH) and acute phase response (turpentine oil-treated rats) revealed that three out of 12 genes (thymidine kinase 1, Jun-D and ADP-ribosylation factor 4) were not affected by the hepatic acute phase reaction but similarly overexpressed in both "oval cell"-dependant and normal liver regeneration. We characterized Jun-D and ADP-ribosylation factors as novel factors upregulated in oval cells and in non-parenchymal liver cells of normally regenerating livers. However, two out of 12 differentially expressed genes were specifically expressed in oval cells: ras-related protein Rab-3b and Ear-2. On protein level, Rab-3b was increased in total liver homogenates and demonstrated only in clusters of oval cells. We postulate that Ear-2 and Rab-3b may represent novel regulatory factors specifically activated in "oval cells".
在某些条件下，肝脏再生可由肝祖细胞（“卵圆细胞”）完成。到目前为止，仅有少数几个因子被确定为受“卵圆细胞”区室独特调控。我们在卵圆细胞增殖大鼠模型（用2-乙酰氨基芴和部分肝切除术处理，AAF + PH）中运用基因芯片分析，与合适的对照模型（AAF处理和假手术或单独AAF处理）相比，鉴定出12个差异表达基因。在正常肝脏再生模型（普通部分肝切除术）和急性期反应模型（松节油处理的大鼠）中的进一步分析显示，12个基因中有3个（胸苷激酶1、Jun-D和ADP-核糖基化因子4）不受肝脏急性期反应影响，但在“卵圆细胞”依赖的肝脏再生和正常肝脏再生中均类似地过度表达。我们将Jun-D和ADP-核糖基化因子鉴定为在卵圆细胞和正常再生肝脏的非实质肝细胞中上调的新因子。然而，12个差异表达基因中有2个在卵圆细胞中特异性表达：ras相关蛋白Rab-3b和Ear-2。在蛋白水平上，Rab-3b在肝脏总匀浆中增加，且仅在卵圆细胞簇中显示。我们推测Ear-2和Rab-3b可能代表在“卵圆细胞”中特异性激活的新调控因子。
