title: Reciprocal regulation of prothrombin secretion and tyrosine aminotransferase induction in hepatocytes.
abstract: Multicellular spheroids of hepatocytes are known to maintain liver functions for a long period. Rat hepatocytes were isolated to form spheroids by rotation culture and immobilized within calcium alginate. Immobilized spheroids had a much higher extent of tyrosine aminotransferase induction, which is one of the liver-specific differentiated functions, than immobilized non-aggregated cells, while the spheroids secreted significantly less prothrombin than non-aggregated cells. Co-culture of hepatocytes and non-parenchymal liver cells in a monolayer enhanced tyrosine aminotransferase induction and suppressed prothrombin secretion, while conditioned medium prepared from non-parenchymal cells greatly stimulated tyrosine aminotransferase induction and suppressed the prothrombin secretion and DNA synthesis in monolayer-cultured hepatocytes. Prothrombin secretion in hepatocytes was subjected to cell-density-dependent regulation. In a similar manner to other growth-related functions, prothrombin secretion was stimulated at low cell density. It has been reported that thrombin activates the zymogen of hepatocyte growth factor activator [Shimomura, T., Kondo, J., Ochiai, M., Naka, D., Miyazawa, K., Morimoto, Y. & Kitamura, N. (1993) J. Biol. Chem. 268, 22,927-22,932]. Therefore, prothrombin secretion could be one of the growth-related functions and involved in wound healing and liver regeneration.
authors.affiliation: Faculty of Pharmaceutical Sciences, Osaka University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yagi
authors.forename: C
authors.initials: C
authors.lastname: Yamada
authors.forename: M
authors.initials: M
authors.lastname: Serada
authors.forename: N
authors.initials: N
authors.lastname: Sumiyoshi
authors.forename: N
authors.initials: N
authors.lastname: Michibayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Miura
authors.forename: T
authors.initials: T
authors.lastname: Mizoguchi
mesh_terms: D000818:Animals; D002452:Cell Count; D017077:Culture Media, Conditioned; D004790:Enzyme Induction; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism*; D008297:Male; D011516:Prothrombin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014444:Tyrosine Transaminase / Q000096:biosynthesis*
chemical_list: D017077:Culture Media, Conditioned; D011516:Prothrombin; D014444:Tyrosine Transaminase