APOPTOSIS EXPRESSION IN CONGENITAL HEPATIC FIBROSIS

Abstract

93 Abstract. Congenital hepatic fibrosis is a rare disease characterized by portal fibrosis and biliary ductular ectasia. The stellate cell is the major source of fibrosis in the liver. Stellate cell action is mediated mainly by serine threonine kinase receptors types I and II. The receptors mediate signal transducer by incompletely defined pathways and result in the programmed cell death or apoptosis. This signal is instrumental in organ development and in the inhibition of epithelial proliferation by TGF β1. The increased expression of TGF β1 and the abnormal distribution of the type I and II receptors in CHF led us to speculate about the extent of apoptosis on hepatocytes and biliary ductular epithelial cells in this classic condition of Ductal Plate Malformation. Methods. Three normal livers, two CHF livers, and two CHF wedge biopsies were used. The Oncor Apoptag Plus In situ detection kit was used (Oncor, Gaithesburg, MD). The method identifies 3′ OH DNA fragments produced by the action of endonuclease in the process of apoptosis. The TdT enzyme (terminal deoxynucleotidyl transferase) that attaches the digoxigenin to the 3′ OH DNA fragments was prepared within 6 hours. The antidigoxigenin fluorescein antibody was then applied and the reaction proceeded for 30 minutes at room temperature in a humidified chamber. Counter staining was then performed with Propidium iodide and the slides were read with a florescent microscope at 494 nm wavelength. Two positive and one negative control were supplies by the manufacturer. Results. Normal liver showed minimal apoptosis as expected. There was an increase in the degree of apoptosis in CHF livers. This may reflect the increased expression of TGF β1 previously described. The ectatic biliary epithelium appears to lack any evidence of apoptosis. Conclusion. The effect of an increased expression of TGF β1 in CHF results in hepatocyte apoptosis in CHF. The increase in apoptosis may eventually lead to a decrease in parenchymal cell mass. The lack of apoptosis in the ectatic biliary epithelium may reflect the lack of TGF β1 receptor II expression and may explain the hyperplasia in this condition.