Liver expression of epidermal growth factor RNA. Rapid increases in immediate-early phase of liver regeneration

The liver exhibits a remarkable capacity to regenerate its mass following partial removal or after injury. Transmembrane receptors for epidermal growth factor (EGF) are highly expressed in liver cells, which quickly respond to this polypeptide mitogen by activating an intrinsically low rate of cell division. Although EGF appears to regulate liver growth, its significance has remained unclear, and only a small change in serum levels can be detected during hepatocellular proliferation. Using a reverse transcription-polymerase chain reaction assay, we report here the novel finding that EGF RNA transcripts are synthesized in a hepatic cell-specific pattern, appearing in hepatocyte and lipocyte cell types. Our data reveal that within 15 min following a 70% liver removal, EGF RNA levels increase > 10-fold and then diminish below basal levels prior to the first wave of regenerative cell division. Immunoanalysis of metabolically labeled hepatocytes shows that EGF accumulates as a large 60-kDa peptide. These results demonstrate that EGF transcription is a previously unrecognized component of hepatic gene expression, and rapid increases in EGF RNA levels in the immediate-early phase of liver regeneration point to EGF as an autocrine factor in the prereplicative hepatic growth program.