DIFFERENTIAL EFFECT OF MICRONODULAR AND BILIARY-CIRRHOSIS ON EPIDERMAL GROWTH-FACTOR RECEPTOR EXPRESSION IN THE RAT

Cirrhosis is characterized by fibrogenesis, hepatocyte necrosis and th e formation of regenerative nodules. Modulation of the epidermal growt h factor receptor is an early event during regeneration. We have recen tly demonstrated alterations in the epidermal growth factor receptor d uring the development of biliary cirrhosis. The aim of the present stu dy was to compare epidermal growth factor receptor distribution, expre ssion and binding in biliary cirrhosis to that occurring in micronodul ar cirrhosis induced by phenobarbital/CCl4 exposition. Biliary cirrhos is and micronodular cirrhosis had similar functional impairment as ass essed by the aminopyrine breath test. Epidermal growth factor receptor binding capacity was reduced in both models (control vs micronodular cirrhosis vs biliary cirrhosis: (mean +/- SD) 60 +/- 22 vs 16 +/- 12 v s 27 +/- 9 fmol/mg protein, p<0.05), while the binding constant was in creased in biliary cirrhosis only. The receptor mass in plasma membran e, determined by Western blotting, was not changed. Distribution of ep idermal growth factor receptor was assessed immunohistochemically on t issue sections. In both models, cytoplasmic staining was decreased and basolateral plasma membrane labeling was maintained. Nuclear localiza tion was found in biliary cirrhosis only. In conclusion, in both model s, cirrhosis induces an alteration in the binding properties, but not in the number of epidermal growth factor receptors in the plasma membr ane. The loss of cytoplasmic epidermal growth factor receptor could re flect alterations in expression and/or in intracellular trafficking. T his is supported by the reduced mRNA steady state levels for epidermal growth factor receptor which were found in both models, presumably re presenting down-regulation. The difference in nuclear labeling indicat es a different regenerative potential of the liver in biliary versus m icronodular cirrhosis. (C) Journal of Hepatology.