EXPRESSION OF CYTOKERATIN-20 IN DEVELOPING RAT-LIVER AND IN EXPERIMENTAL-MODELS OF DUCTULAR AND OVAL CELL-PROLIFERATION

Backgound/Aiins: Recently a novel type of cytokeratin (CK) has been ad ded to the classical catalog of CKs as CK20. The aim of the present st udy was to examine the immunoreactivity for CK20 in normal and develop ing rat liver and in experimental models of bile ductular and oval cel l proliferation. Methods: Eighty-five Fischer rats, subdivided into fi ve groups, were utilized in this study: fetal rats, ranging from day 1 0 to day 21 of gestation; newborn-neonatal rats, from 2 h to 10 days o f age; bile duct ligated (BDL) rats; alpha-naphthyl-isothiocyanate (AN IT)-treated rats; and rats fed a choline-deficient diet containing N-2 Fluorenylacetamide (CD-AAF rats). Frozen sections from each liver wer e stained with the CK20 specific monoclonal antibody IT-K(S)20.10. Res ults: The present study shows that CK20 is a ''bile duct type'' CK. In the fetal rat, CK20 appears late during intrahepatic bile duct develo pment, at day 20 of gestation. A marked increase in CK20 expression oc curs after birth, suggesting that intrahepatic bile duct maturation co ntinues after birth and that CK20 may be considered as a ''maturation' ' marker of the biliary tree. In BDL rats and in ANIT-treated animals, immunoreactivity of bile ductules for CK20 was strikingly heterogeneo us. A variable number of proliferating biliary cells were weakly posit ive or negative for CK20 and their number increased with the duration of the obstruction or ANIT treatment. In CD-AAF-treated rats, we found a uniform staining of proliferating oval cells for CK20. This finding is in contrast with the observation in BDL and in ANIT groups, and su ggests the existence of different mechanisms regulating the proliferat ion and differentiation of biliary cells under those conditions. Concl usions: In rat liver, CK20 may be added to the list of ''bile duct typ e'' cytokeratins. During development, CK20 expression may be related t o the maturation stage of the biliary tree. Typical ductular prolifera tion induced by BDL or ANIT feeding clearly differs from the oval cell proliferation in the CD-AAF model in terms of immunoreactivity for CK 20.