Role of c-kit receptor tyrosine kinase in development of oval cells in the rat 2-acetylaminofluorene partial hepatectomy model
Role of c-kit receptor tyrosine kinase in development of oval cells in the rat 2-acetylaminofluorene partial hepatectomy model
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DOI：
10.1002/hep.510290304
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发表时间：
1999-03-01
期刊：
影响因子：
13.5
通讯作者：
Terada, N
中科院分区：
文献类型：
--
作者：
Matsusaka, S;Tsujimura, T;Terada, N
在大鼠2-乙酰氨基荧光/部分肝切除（AAF/PH）模型中发育的卵形细胞表达c-hit受体酪氨酸激酶（KIT）及其配体干细胞因子（SCF），我们用Ws/Ws大鼠研究了SCF/KIT系统在卵形细胞发育中的作用，这些大鼠的c-hie激酶活性由于激酶结构域的小缺失而严重受损。在AAF/PH模型的第7、9和13天，与正常（+/+）对照大鼠相比，Ws/Ws大鼠卵形细胞的发育明显受到抑制。然而，Ws/Ws大鼠卵形细胞表达的卵形细胞标记蛋白如胎蛋白（AFP）、细胞角蛋白-19 （CK-19）和flt-3受体酪氨酸激酶与+/+大鼠相似。此外，用[H-3]-胸苷标记和Ki-67免疫染色表明，Ws/Ws大鼠的卵形细胞增殖活性与+/+大鼠相当。目前的结果表明，SCF/KIT系统的信号转导在卵形细胞的发育中起着至关重要的作用，至少在大鼠AAF/PH模型中是如此，并且表明KIT介导的信号转导在决定卵形细胞的表型和增殖活性中仅起很小的作用。
Oval cells that develop in the rat 2-acetylaminofluorene/partial hepatectomy (AAF/PH) model express the c-hit receptor tyrosine kinase (KIT) and its ligand, stem cell factor (SCF), We investigated the role of the SCF/KIT system in the development of oval cells using Ws/Ws rats, whose c-hie kinase activity was severely impaired owing to a small deletion in the kinase domain. On days 7, 9, and 13 after PH in the AAF/PH model, the development of oval cells was remarkably suppressed in Ws/Ws rats when compared with that of the control normal (+/+) rats. However, oval cells that developed in Ws/Ws rats expressed marker proteins of oval cells, such as cw-fetoprotein (AFP), cytokeratin-19 (CK-19), and flt-3 receptor tyrosine kinase, similar to those of +/+ rats. Furthermore, labeling with [H-3]-thymidine and immunostaining of Ki-67 showed that the proliferative activity of oval cells that developed in Ws/Ws rats was comparable with that of +/+ rats. The present results indicate that the signal transduction of the SCF/KIT system plays a crucial role in the development of oval cells, at least, in the rat AAF/PH model, and suggest that KIT-mediated signal transduction plays only a small role in determining the phenotype and in the proliferative activity of oval cells.