Nakamura T, Fujii T, Ichihara A
Institute for Enzyme Research, University of Tokushima.
J Biochem. 1988 Apr;103(4):700-6. doi: 10.1093/oxfordjournals.jbchem.a122332.
Hepatocytes from neonatal rats of 0 to 3 days old grew actively in primary culture without added serum or growth factors. In these culture conditions, growth of hepatocytes decreased progressively with increase in age of the rats from which they were isolated, and hepatocytes from rats of 2 weeks old showed scarcely any growth. Actively growing hepatocytes were found to secrete a growth factor that promoted their growth and that of Swiss 3T3 cells, but not that of adult hepatocytes. This growth factor in conditioned medium of growing hepatocytes was heat- and acid-stable, but sensitive to trypsin, and had a molecular weight of over 10,000. It did not inhibit the binding of [125I]epidermal growth factor to its receptor, and its growth promoting activity was not inhibited by monoclonal antibody against insulin-like growth factor II. Therefore, it seems to be a new growth factor. These results, together with previous findings (Nakamura, T., Nagao, M., & Ichihara, A. (1987) Exp. Cell Res. 169, 1-14) demonstrated a reciprocal relation between growth and maturation of neonatal hepatocytes during development, like that of adult cells, but indicated that unlike growth of the latter, growth of neonatal cells is induced by an autocrine mechanism.
0至3日龄新生大鼠的肝细胞在无添加血清或生长因子的原代培养中生长活跃。在这些培养条件下，肝细胞的生长随着所分离大鼠年龄的增加而逐渐下降，2周龄大鼠的肝细胞几乎没有生长。发现活跃生长的肝细胞分泌一种生长因子，该因子能促进其自身以及瑞士3T3细胞的生长，但不能促进成年肝细胞的生长。生长中的肝细胞条件培养基中的这种生长因子对热和酸稳定，但对胰蛋白酶敏感，分子量超过10000。它不抑制[125I]表皮生长因子与其受体的结合，其促生长活性也不受抗胰岛素样生长因子II单克隆抗体的抑制。因此，它似乎是一种新的生长因子。这些结果与先前的发现（Nakamura, T., Nagao, M., & Ichihara, A. (1987) Exp. Cell Res. 169, 1 - 14）一起表明，在发育过程中，新生肝细胞的生长和成熟之间存在一种相互关系，类似于成年细胞，但表明与成年细胞的生长不同，新生细胞的生长是由自分泌机制诱导的。
