大鼠胎儿肝细胞对肝细胞生长因子的生长刺激反应：c-myc和c-fos表达的调节

Growth stimulation of rat fetal hepatocytes in response to hepatocyte growth factor: modulation of c-myc and c-fos expression.

作者信息

Fabregat I, de Juan C, Nakamura T, Benito M

机构信息

Departamento de Bioquímica y Biología Molecular, Centro Mixto C.S.I.C./U.C.M., Facultad de Farmacia, Ciudad Universitaria, Madrid, Spain.

出版信息

Biochem Biophys Res Commun. 1992 Dec 15;189(2):684-90. doi: 10.1016/0006-291x(92)92255-v.

DOI:10.1016/0006-291x(92)92255-v

PMID:1281997

Abstract

Hepatocyte growth factor, which is a potent growth factor for primary cultured adult hepatocytes, strongly stimulated DNA synthesis of rat fetal (20-day of gestation) hepatocytes. Its mitogenic capacity, measured as (3H)-thymidine incorporation into acid precipitable material was dose dependent, being detectable at 1 ng/ml and maximal at 5 ng/ml. Over 15% of the cells entered into S-phase and mitosis as judged by flow cytometric analysis of the cell cycle. HGF had additive effects with transforming growth factor-alpha, whereas transforming growth factor-beta strongly inhibited DNA synthesis of fetal hepatocytes stimulated by HGF. HGF induced c-fos and c-myc expression in a time-dependent manner, with a maximum at 30 min for c-fos and 8 h for c-myc. These results suggest that HGF may act as a proliferative factor during fetal liver growth.

摘要

肝细胞生长因子是原代培养的成年肝细胞的一种强效生长因子，它能强烈刺激大鼠胎肝（妊娠20天）细胞的DNA合成。其促有丝分裂能力，以（3H）-胸苷掺入酸不溶性物质来衡量，呈剂量依赖性，在1 ng/ml时可检测到，在5 ng/ml时达到最大值。通过细胞周期的流式细胞术分析判断，超过15%的细胞进入S期和有丝分裂期。肝细胞生长因子与转化生长因子-α有相加作用，而转化生长因子-β强烈抑制由肝细胞生长因子刺激的胎肝细胞的DNA合成。肝细胞生长因子以时间依赖性方式诱导c-fos和c-myc表达，c-fos在30分钟时达到最大值，c-myc在8小时时达到最大值。这些结果表明，肝细胞生长因子可能在胎儿肝脏生长过程中作为一种增殖因子发挥作用。