Mitogenic effects of hepatic stimulator substance on cultured nonparenchymal liver epithelial cells

Sanjeev Gupta, Douglas R. Labrecque, David A. Shafritz

Research output: Contribution to journalArticle

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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 < 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-β1 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-β1 abrogated the inhibitory effect of transforming growth factor-β1. 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.

Original languageEnglish (US)
Pages (from-to)485-491
Number of pages7
JournalHepatology
Volume15
Issue number3
StatePublished - Mar 1992

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Epithelial Cells
Liver
Hepatocytes
Transforming Growth Factors
S Phase
Thymidine
hepatic stimulator substance
Neurokinin A
Butyrates
G2 Phase
DNA
Cell Lineage
Cell Cycle Checkpoints
Epidermal Growth Factor
Cell Division
Hepatocellular Carcinoma
Flow Cytometry
Cell Line

ASJC Scopus subject areas

  • Hepatology

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Mitogenic effects of hepatic stimulator substance on cultured nonparenchymal liver epithelial cells. / Gupta, Sanjeev; Labrecque, Douglas R.; Shafritz, David A.

In: Hepatology, Vol. 15, No. 3, 03.1992, p. 485-491.

Research output: Contribution to journalArticle

Gupta, Sanjeev ; Labrecque, Douglas R. ; Shafritz, David A. / Mitogenic effects of hepatic stimulator substance on cultured nonparenchymal liver epithelial cells. In: Hepatology. 1992 ; Vol. 15, No. 3. pp. 485-491.
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