Fujio K, Hu Z, Evarts R P, Marsden E R, Niu C H, Thorgeirsson S S
Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA.
Exp Cell Res. 1996 May 1;224(2):243-50. doi: 10.1006/excr.1996.0134.
Stem cell factor and its receptor c-kit constitute an important signal transduction system implicated in survival, proliferation, and differentiation of stem cells in hematopoiesis, gametogenesis, and melanogenesis. In the present study we used both immunocytochemical methods and Western analysis to demonstrate the presence of this cytokine/receptor system in both embryonic and adult rat liver. Stem cell factor was present in the ductular cells around the portal vein during the late embryonic stage of the liver. In the adult liver both bile ducts and bile ductules were positive for stem cell factor and c-kit. When the activation of the liver stem cell compartment was induced by combining administration of acetylaminofluorene and partial hepatectomy, both stem cell factor and c-kit were expressed in the infiltrating oval cell population, but absent in the newly formed basophilic hepatocytes. Activation of oval cell proliferation following administration Of D-galactosamine also produced a similar but less prominent increase in the level of the stem cell factor. Our data suggest that the stem cell factor/c-kit signal transduction system is involved in the development of bile ducts and that it may also be an important member of the growth factor/receptor systems associated with the biology of liver stem cells.
干细胞因子及其受体c-kit构成了一个重要的信号转导系统,该系统与造血、配子发生和黑色素生成过程中干细胞的存活、增殖及分化有关。在本研究中,我们使用免疫细胞化学方法和蛋白质印迹分析来证明这种细胞因子/受体系统在胚胎期和成年大鼠肝脏中的存在。在肝脏胚胎发育后期,干细胞因子存在于门静脉周围的小胆管细胞中。在成年肝脏中,胆管和胆小管的干细胞因子和c-kit均呈阳性。当联合给予乙酰氨基芴和部分肝切除诱导肝干细胞区室激活时,干细胞因子和c-kit均在浸润的卵圆细胞群体中表达,但在新形成的嗜碱性肝细胞中不存在。给予D-半乳糖胺后卵圆细胞增殖的激活也使干细胞因子水平产生了类似但不太明显的升高。我们的数据表明,干细胞因子/c-kit信号转导系统参与胆管的发育,并且它可能也是与肝干细胞生物学相关的生长因子/受体系统的重要成员。