Russell W E
Endocrine-Metabolic Unit, Massachusetts General Hospital, Boston, Massachusetts.
J Cell Physiol. 1988 May;135(2):253-61. doi: 10.1002/jcp.1041350212.
Subpicomolar concentrations of human platelet-derived transforming growth factor beta (TGF-beta) inhibited growth factor-stimulated DNA synthesis in primary cultures of adult rat hepatocytes. This inhibition was not the result of changes in the size of intracellular pools of 3H-thymidine and was not dependent on the state of confluence of the cells. A 24-hr exposure to TGF-beta either before or after insulin/EGF stimulation was as inhibitory on DNA synthesis between 48 and 72 hr of culture as was TGF-beta present throughout 72 hr of culture. From 12 hr in culture to 24 hr, hepatocyte EGF binding sites dropped from about 230,000 to 85,000 per cell with no significant change in Kd, but with a loss in capacity for EGF-induced receptor down-regulation. Maximally inhibitory concentrations of TGF-beta did not compete with EGF for the EGF receptor, and a 4- to 24-hr exposure to TGF-beta did not alter subsequent EGF binding. Coincubation of hepatocytes with TGF-beta and EGF did not influence the 60% reduction in EGF binding sites produced by EGF alone. In addition, TGF-beta did not prevent EGF-induced autophosphorylation of the 170,000 dalton EGF receptor in membranes from whole liver. Our studies suggest that TGF-beta regulates hepatocyte growth independently of changes in EGF receptor number, ligand affinity, or postbinding autophosphorylation.
亚皮摩尔浓度的人血小板衍生转化生长因子β（TGF-β）可抑制成年大鼠肝细胞原代培养物中生长因子刺激的DNA合成。这种抑制作用并非3H-胸腺嘧啶核苷细胞内池大小变化的结果，也不依赖于细胞的汇合状态。在胰岛素/表皮生长因子（EGF）刺激之前或之后24小时暴露于TGF-β，对培养48至72小时期间DNA合成的抑制作用，与在整个72小时培养过程中都存在TGF-β时的抑制作用相同。从培养12小时到24小时，肝细胞EGF结合位点从每个细胞约230,000个降至85,000个，解离常数（Kd）无显著变化，但EGF诱导的受体下调能力丧失。TGF-β的最大抑制浓度不会与EGF竞争EGF受体，并且4至24小时暴露于TGF-β不会改变随后的EGF结合。肝细胞与TGF-β和EGF共同孵育，不会影响单独使用EGF时产生的EGF结合位点60%的减少。此外，TGF-β不会阻止全肝细胞膜中170,000道尔顿EGF受体的EGF诱导的自磷酸化。我们的研究表明，TGF-β独立于EGF受体数量、配体亲和力或结合后自磷酸化的变化来调节肝细胞生长。
