Mead J E, Fausto N
Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02912.
Proc Natl Acad Sci U S A. 1989 Mar;86(5):1558-62. doi: 10.1073/pnas.86.5.1558.
We investigated whether transforming growth factor alpha (TGF-alpha) is involved in hepatocyte growth responses both in vivo and in culture. During liver regeneration after partial hepatectomy in rats, TGF-alpha mRNA increased; it reached a maximum (approximately 9-fold higher than normal) at the peak of DNA synthesis. The message and the peptide were localized in hepatocytes and found in higher amounts in hepatocytes obtained from regenerating liver. TGF-alpha caused a 13-fold elevation of DNA synthesis in hepatocytes in primary culture and was slightly more effective than epidermal growth factor. TGF-beta blocked TGF-alpha stimulation when added either simultaneously with TGF-alpha or a day later. TGF-alpha message increased in hepatocytes stimulated to undergo DNA synthesis by TGF-alpha or epidermal growth factor, and the peptide was detected in the culture medium by RIA. In the regenerating liver, the increase in TGF-alpha mRNA during the first day after partial hepatectomy coincided with an increase in epidermal growth factor/TGF-alpha receptor mRNA and a decrease (already reported) in the number of these receptors. We conclude that TGF-alpha may function as a physiological inducer of hepatocyte DNA synthesis during liver regeneration by means of an autocrine mechanism and that its stimulatory effects in this growth process are balanced by the inhibitory action of TGF-beta 1.
我们研究了转化生长因子α（TGF-α）是否在体内和体外培养中参与肝细胞生长反应。在大鼠部分肝切除术后的肝脏再生过程中，TGF-α mRNA增加；在DNA合成高峰期达到最大值（比正常水平高约9倍）。该信息和肽定位于肝细胞中，并且在从再生肝脏获得的肝细胞中含量更高。TGF-α使原代培养的肝细胞中的DNA合成提高了13倍，并且比表皮生长因子略有效。当与TGF-α同时添加或在一天后添加时，TGF-β会阻断TGF-α的刺激作用。TGF-α信息在受到TGF-α或表皮生长因子刺激而进行DNA合成的肝细胞中增加，并且通过放射免疫分析在培养基中检测到该肽。在再生肝脏中，部分肝切除术后第一天TGF-α mRNA的增加与表皮生长因子/TGF-α受体mRNA的增加以及这些受体数量的减少（已报道）同时发生。我们得出结论，TGF-α可能通过自分泌机制在肝脏再生过程中作为肝细胞DNA合成的生理诱导剂起作用，并且其在该生长过程中的刺激作用被TGF-β1的抑制作用所平衡。
