Keratinocyte growth factor and fibroblast growth factor action on DNA synthesis in rat and human hepatocytes: modulation by heparin.
Keratinocyte growth factor (KGF/FGF-7) is a member of the fibroblast growth factor (FGF) superfamily. Unlike other members of the family, the biological activity of KGF appears to be restricted to epithelial cells. Here we have tested the activity of KGF, acidic fibroblast growth factor (aFGF), and basic fibroblast growth factor (bFGF) on normal adult rat and human hepatocytes and their modulation by heparin. Although more modest than the growth response to epidermal growth factor (EGF) and hepatocyte growth factor (HGF), recombinant KGF enhanced DNA synthesis in rat hepatocytes by two- to threefold. This stimulation occurred in the absence of serum and of other exogenous growth factors. Addition of heparin inhibited the KGF response. Although basic FGF showed little activity on rat hepatocytes, acidic FGF stimulated DNA synthesis by approximately twofold and was substantially enhanced by heparin. In contrast to rat cells, human hepatocytes consistently failed to respond to KGF, aFGF, or bFGF with or without heparin, under conditions where EGF and HGF stimulated DNA synthesis up to sixfold. These results indicate that KGF is capable of acting as a complete mitogen for rat hepatocytes in culture and that the activity is consistent with expression by these cells of a type II FGF receptor subtype, the KGF receptor. These observations suggest that KGF/aFGF together with proteoglycans may help regulate rat but not human liver growth.
Strain
A J
AJ
School of Biochemistry, University of Birmingham, Edgbaston, United Kingdom.
McGuinness
G
G
Rubin
J S
JS
Aaronson
S A
SA
D000328:Adult; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
C496453:FGF7 protein, human; C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006493:Heparin; D004247:DNA