THE EFFECT OF RETINOIC ACID ON THE REESTABLISHMENT OF DIFFERENTIATED HEPATOCYTE PHENOTYPE IN PRIMARY CULTURE

The usefulness of cultured hepatocytes is limited by the gradual loss of their typical physiological functions that occurs in vitro, mainly due to the absence of microenviromental conditions found in vivo. In t his study we describe the effect of retinoic acid on the re-establishm ent of morphological characteristics and on the reorganization of the cytoskeletal network in cultured rat hepatocytes. Results obtained dem onstrate that retinoic acid can influence hepatocyte differentiation, as regards the recovery of cell polarity, polyhedric shape and reforma tion of bile canaliculi and junctional complexes. The main target of t his action appears to be the cytoarchitecture of cytoskeletal componen ts, particularly cytokeratin filaments, which regain the configuration present in intact liver. The reorganization of the intermediate filam ents does not seem to be dependent on the induction of higher levels o f cytokeratin proteins, but rather appears to be due to post-translati onal regulation. The effect of retinoic acid on the cytoskeletal organ ization could determine the stabilization of intercellular contacts by means of junctions, leading to the appearance of morpho-functional ch aracteristics typical of well-differentiated hepatocytes.