title: Mitogenic effects of hepatic stimulator substance on cultured nonparenchymal liver epithelial cells.
abstract: We determined whether hepatic stimulator substance shares its mitogenic specificity for hepatocytes with nonparenchymal epithelial cells in the hepatocyte lineage. Cell lines designated HTC (derived from a rat hepatoma known to respond to hepatic stimulator substance) and FNRL, K-16 and K-22 (derived from rat liver nonparenchymal epithelial cells) were used. After exposure to hepatic stimulator substance, [3H]-thymidine incorporation into DNA was significantly increased (p less than 0.001) in HTC, FNRL and K-16 cells, but not in K-22 cells. Fluorescence-activated cell sorting demonstrated that the mitogenic response to hepatic stimulator substance was associated with a greater proportion of cells entering the S phase. Epidermal growth factor, alone or in combination with hepatic stimulator substance, had no significant mitogenic effect on FNRL cells, but exposure of these cells to transforming growth factor-beta 1 inhibited [3H]-thymidine incorporation into DNA and reduced the proportion of cells in the S and G2/M phases. Simultaneous exposure of FNRL cells to hepatic stimulator substance and transforming growth factor-beta 1 abrogated the inhibitory effect of transforming growth factor-beta 1. Comparison of butyrate-synchronized HTC cells with hepatic stimulator substance-treated HTC cells showed that S-phase progression in these conditions was different, with no intervening cell cycle arrest after treatment with hepatic stimulator substance. Mitogenic stimulation of FNRL and K-16 cells with the liver-specific growth factor hepatic stimulator substance suggests that these cells are of hepatocyte lineage. These results strengthen the evidence for a possible link between hepatocytes and nonparenchymal liver epithelial cells during liver biogenesis and differentiation.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: S
authors.initials: S
authors.lastname: Gupta
authors.forename: D R
authors.initials: DR
authors.lastname: LaBrecque
authors.forename: D A
authors.initials: DA
authors.lastname: Shafritz
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005434:Flow Cytometry; D006133:Growth Substances / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008934:Mitogens / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens; D010455:Peptides; D016212:Transforming Growth Factor beta; C073456:hepatic stimulator substance; D004815:Epidermal Growth Factor