Skrtic S, Ekberg S, Wallenius V, Enerbäck S, Hedin L, Jansson J O
Research Center for Endocrinology and Metabolism, Sahlgrenska University Hospital, University of Göteborg, Sweden.
J Hepatol. 1997 Nov;27(5):903-11. doi: 10.1016/s0168-8278(97)80329-7.
BACKGROUND/AIMS: The proliferation rate of adult rat liver is normally very low. It is markedly enhanced during compensatory regeneration, e.g. after partial hepatectomy, or after administration of certain growth promoters, e.g. cyproterone acetate. These two types of liver cell proliferation appear to differ, since the expression of immediate early genes is induced during compensatory regeneration but not after cyproterone acetate treatment. The transcription factor C/EBP alpha, which has been associated with hepatocyte differentiation and growth arrest, is suppressed during compensatory regeneration. In contrast, C/EBP beta, associated with acute phase reaction, is increased during regeneration. We have investigated the effects of the liver growth promoter cyproterone acetate on the hepatic expression of C/EBP alpha and C/EBP beta.
Adult male rats received either cyproterone acetate treatment or were subjected to partial hepatectomy. Livers were obtained at different time intervals for measurement of C/EBP alpha and C/EBP beta mRNA with solution hybridization/RNAse protection assay, and C/EBP alpha and C/EBP beta content with immunoblotting.
The levels of both C/EBP alpha and C/EBP beta mRNA and the corresponding immunoreactivities were unchanged 2-48 h after injection of cyproterone acetate. The levels of C/EBP alpha mRNA and immunoreactivity were significantly suppressed 10-18 h and 18-26 h after partial hepatectomy, respectively. The levels of C/EBP beta mRNA and immunoreactivity were enhanced during compensatory regeneration 2 h after partial hepatectomy.
Liver cell proliferation during regeneration, but not in response to cyproterone acetate treatment, is associated with changes in C/EBP alpha and C/EBP beta expression. This further supports the notion that changes in expression of transcription factors during liver growth in vivo are dependent on the growth inducer.
背景/目的:成年大鼠肝脏的增殖速率通常非常低。在代偿性再生过程中,例如部分肝切除术后,或给予某些生长促进剂(如醋酸环丙孕酮)后,其增殖速率会显著提高。这两种类型的肝细胞增殖似乎有所不同,因为即时早期基因的表达在代偿性再生过程中被诱导,但在醋酸环丙孕酮处理后则不会。与肝细胞分化和生长停滞相关的转录因子C/EBPα在代偿性再生过程中受到抑制。相比之下,与急性期反应相关的C/EBPβ在再生过程中增加。我们研究了肝脏生长促进剂醋酸环丙孕酮对肝脏中C/EBPα和C/EBPβ表达的影响。
成年雄性大鼠接受醋酸环丙孕酮处理或进行部分肝切除术。在不同时间间隔获取肝脏,通过溶液杂交/RNA酶保护试验测量C/EBPα和C/EBPβ mRNA水平,通过免疫印迹法测量C/EBPα和C/EBPβ含量。
注射醋酸环丙孕酮后2 - 48小时,C/EBPα和C/EBPβ mRNA水平以及相应的免疫反应性均未改变。部分肝切除术后10 - 18小时和18 - 26小时,C/EBPα mRNA水平和免疫反应性分别显著降低。部分肝切除术后2小时的代偿性再生过程中,C/EBPβ mRNA水平和免疫反应性增强。
再生过程中的肝细胞增殖,而非对醋酸环丙孕酮处理的反应,与C/EBPα和C/EBPβ表达的变化相关。这进一步支持了体内肝脏生长过程中转录因子表达变化取决于生长诱导剂的观点。