Strömblad S, Andersson G
Department of Pathology, Karolinska Institute, Huddinge University Hospital, Sweden.
Exp Cell Res. 1993 Feb;204(2):321-8. doi: 10.1006/excr.1993.1039.
Transcriptional and post-transcriptional regulation of hepatic expression of the epidermal growth factor receptor (EGF-R) and its autocrine ligand, transforming growth factor-alpha (TGF-alpha), were analyzed during liver regeneration. The EGF-R mRNA levels were about twofold induced at 3 h after hepatectomy, caused by transcriptional activation. This was immediately followed by a decrease, reaching a low at half the initial level after 18 h, due to a decreased transcriptional rate. TGF-alpha mRNA expression was detected in normal liver using solution hybridization analysis. Concurrent with the decrease in EGF receptors, an increase of the TGF-alpha mRNA level occurred, starting at 6 h after hepatectomy and peaking at twice the initial TGF-alpha mRNA level after 12-24 h. For TGF-alpha, however, no increase in the rate of gene transcription could be detected. TGF-alpha and EGF competed for binding to the same hepatic receptor in normal as well as in regenerating liver. TGF-alpha bound to a similar number of binding sites as EGF in both control and 18-h posthepatectomy livers, but with 4-5 times lower affinity than EGF. At 18 h posthepatectomy, the number of binding sites was reduced to about 55% for both ligands. When the subcellular distribution of endocytosed 125I-labeled TGF-alpha was compared with that of 125I-labeled EGF, no differences were observed, and furthermore, no changes were observed in the subcellular distribution of 125I-labeled TGF-alpha during liver regeneration. The distinct and coordinate regulation of the two interactors, EGF-R and TGF-alpha, suggests that the EGF-receptor system may be functionally involved in the different phases of the prereplicative growth stimulatory process during liver regeneration.
在肝脏再生过程中，对表皮生长因子受体（EGF-R）及其自分泌配体转化生长因子-α（TGF-α）在肝脏中的表达进行了转录和转录后调控分析。肝切除术后3小时，EGF-R mRNA水平因转录激活而诱导增加约两倍。随后立即下降，由于转录速率降低，在18小时后降至初始水平的一半。使用溶液杂交分析在正常肝脏中检测到TGF-α mRNA表达。与EGF受体减少同时发生的是，TGF-α mRNA水平从肝切除术后6小时开始增加，并在12 - 24小时后达到初始TGF-α mRNA水平的两倍峰值。然而，对于TGF-α，未检测到基因转录速率的增加。在正常肝脏和再生肝脏中，TGF-α和EGF竞争与相同的肝脏受体结合。在对照肝脏和肝切除术后18小时的肝脏中，TGF-α与EGF结合的位点数量相似，但亲和力比EGF低4 - 5倍。在肝切除术后18小时，两种配体的结合位点数量均减少至约55%。当比较内吞的125I标记的TGF-α与125I标记的EGF的亚细胞分布时，未观察到差异，此外，在肝脏再生过程中125I标记的TGF-α的亚细胞分布也未观察到变化。EGF-R和TGF-α这两种相互作用分子的独特且协同调控表明，EGF受体系统可能在肝脏再生的复制前生长刺激过程的不同阶段发挥功能作用。
