Nishikawa Y, Wang M, Carr B I
Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pennsylvania 15213, USA.
J Cell Physiol. 1998 Sep;176(3):612-23. doi: 10.1002/(SICI)1097-4652(199809)176:3<612::AID-JCP18>3.0.CO;2-0.
To clarify the role of transforming growth factor-beta (TGF-beta) and its receptors in hepatocyte growth, we studied the expression of TGF-beta1 and its receptors and the sensitivity to growth inhibition by TGF-beta1 protein in rat hepatocytes derived from resting and regenerating livers. In hepatocytes derived from resting livers, mRNAs for TGF-beta type II receptor (TbetaR-II), insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-II/M-6-PR), and TGF-beta1 increased with time in primary culture. The cell surface TGF-beta receptor proteins (TbetaR-I, II, and III), examined by the receptor affinity-labeling assay using 125I-TGF-beta1, also increased, especially after 48 hr of culture. Hepatocytes were more sensitive to inhibition of DNA synthesis, when the TGF-beta1 protein was added at later times in culture, corresponding to the presence of increased TGF-beta receptors. In hepatocytes from regenerating livers after a partial hepatectomy (PH), an increase of TbetaR-I, TbetaR-II, TbetaR-III, IGF-II/M-6-PR, and TGF-beta1 mRNAs was found, compared with hepatocytes from resting livers. Similarly, using TGF-beta receptor affinity-labeling assay, hepatocytes from PH livers were found to have an increase in TbetaR-I, II, and III proteins, with a peak at 4 days post-PH, compared with hepatocytes from resting livers. When TGF-beta1 protein was added for a short period (6 or 24 hr) after cell attachment to hepatocyte cultures, it inhibited DNA synthesis more effectively in hepatocytes from regenerating compared with resting livers. Our results show that hepatocyte TGF-beta receptors and sensitivity to growth inhibition by TGF-beta1 protein change together and are modulated during liver regeneration, as well as during the conditions of primary culture.
为阐明转化生长因子-β（TGF-β）及其受体在肝细胞生长中的作用，我们研究了TGF-β1及其受体的表达，以及来自静止和再生肝脏的大鼠肝细胞对TGF-β1蛋白生长抑制的敏感性。在源自静止肝脏的肝细胞中，原代培养时II型TGF-β受体（TβR-II）、胰岛素样生长因子-II/甘露糖6-磷酸受体（IGF-II/M-6-PR）和TGF-β1的mRNA随时间增加。通过使用125I-TGF-β1的受体亲和标记试验检测的细胞表面TGF-β受体蛋白（TβR-I、II和III）也增加，尤其是在培养48小时后。当在培养后期添加TGF-β1蛋白时，肝细胞对DNA合成抑制更敏感，这与TGF-β受体增加的情况相对应。在部分肝切除（PH）后再生肝脏的肝细胞中，与静止肝脏的肝细胞相比，发现TβR-I、TβR-II、TβR-III、IGF-II/M-6-PR和TGF-β1的mRNA增加。同样，使用TGF-β受体亲和标记试验，发现与静止肝脏的肝细胞相比，PH肝脏的肝细胞中TβR-I、II和III蛋白增加，在PH后4天达到峰值。当在肝细胞培养物细胞贴壁后短时间（6或24小时）添加TGF-β1蛋白时，与静止肝脏的肝细胞相比，它对再生肝脏的肝细胞中DNA合成的抑制更有效。我们的结果表明，肝细胞TGF-β受体和对TGF-β1蛋白生长抑制的敏感性共同变化，并在肝脏再生以及原代培养条件下受到调节。
