Transformed fat storing cells inhibit the proliferation of cultured hepatocytes by secretion of transforming growth factor beta.
Conditioned medium from secondary cultures of fat storing cells (transformed fat storing cells) inhibits replicative (hydroxyurea-sensitive) DNA synthesis dose-dependently in primary cultures of hepatocytes stimulated in vitro by transforming growth factor (TGF) alpha. Similarly, [3H]thymidine incorporation into the DNA of hepatocytes from the regenerating rat liver is reduced by about 70% by fat storing, cell conditioned medium. Medium which had been transiently acidified was more potent than native medium. It displaced [125I]TGF-beta from binding sites on the hepatocyte surface and the inhibitory activity was completely blocked by anti-TGF-beta antibodies. From binding studies, a TGF-beta concentration of 1.8 +/- 0.4 ng/ml conditioned medium produced by 2 X 10(5) cells per 24 h was estimated. Transformed, but not primary, cultures of fat storing cells at an early state produce and secrete TGF-beta, which reduces hepatocellular proliferation significantly.
Department of Clinical Chemistry, Philipps University, Marburg, Federal Republic of Germany.
D H
DH
Meyer
M G
MG
Bachem
A M
AM
Gressner
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D008055:Lipids / Q000032:analysis*; D008099:Liver / Q000032:analysis / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism; D015291:Transforming Growth Factors / Q000378:metabolism / Q000502:physiology*; D014316:Tritium / Q000378:metabolism
D008055:Lipids; D014316:Tritium; D015291:Transforming Growth Factors; D004247:DNA; D013936:Thymidine