Ichihara A
Institute for Enzyme Research, University of Tokushima, Japan.
Dig Dis Sci. 1991 Apr;36(4):489-93. doi: 10.1007/BF01298881.
Mature hepatocytes in primary culture express most of the functions and hormonal responsiveness seen in normal liver studied in vivo. The growth of hepatocytes in culture is regulated by various growth factors. We have identified a hepatocyte growth factor that is isolated from rat platelets. We found that rat platelets also contain a growth inhibitor, transforming growth factor-beta which is secreted as a latent molecule. Its latency is due to its binding with a masking protein. Growth of hepatocytes is also suppressed by interleukin-1 (IL-1) and IL-6. Moreover, the growth and functions of liver cells in culture are regulated reciprocally by cell density: at higher cell density liver-specific functions are expressed and growth is suppressed, whereas the opposite situation is observed at lower cell density. In contrast, neonatal hepatocytes in culture grow autonomously without a requirement for added hormones. This autonomous growth is due to an autocrine mechanism in which the cells secrete one or more growth factors into the culture medium. However, this autonomous growth ceases one week after birth at a time when the cells begin to express differentiated characteristics. Based upon these data, the mechanisms of liver regeneration, differentiation, and hepatocarcinogenesis are discussed.
原代培养的成熟肝细胞表现出在体内研究的正常肝脏中所见到的大部分功能和激素反应性。培养的肝细胞生长受多种生长因子调控。我们已鉴定出一种从大鼠血小板中分离出的肝细胞生长因子。我们发现大鼠血小板还含有一种生长抑制剂——转化生长因子-β，它以无活性分子形式分泌。其无活性是由于它与一种封闭蛋白结合。白细胞介素-1（IL-1）和白细胞介素-6也会抑制肝细胞生长。此外，培养的肝细胞的生长和功能受细胞密度的相互调控：在较高细胞密度时，肝脏特异性功能得以表达且生长受到抑制，而在较低细胞密度时则观察到相反情况。相比之下，培养的新生肝细胞自主生长，无需添加激素。这种自主生长归因于一种自分泌机制，即细胞向培养基中分泌一种或多种生长因子。然而，这种自主生长在出生一周后停止，此时细胞开始表现出分化特征。基于这些数据，对肝脏再生、分化和肝癌发生的机制进行了讨论。
