A novel chimeric fibroblast growth factor for liver parenchymal cells.
Although fibroblast growth factor 1 (FGF-1) (formerly known as acidic FGF) but not FGF-2 (or basic FGF), has been suggested to play a pathophysiological role in liver regeneration, its clinical application has been restricted by its limited mitogenecity and heparin dependence. We report here that a chimeric human FGF protein, FGF-C(1211), is a heparin-independent potent mitogen for liver parenchymal cells both in vitro and in vivo. In the presence of serum and physiological concentration of insulin, FGF-C(1211) by itself induces as much as 55% of hepatocytes in culture to proliferate and up to 88% when used in combination with hepatocyte growth factor or epidermal growth factor. Furthermore, hepatocytes nuclear labeling in vivo with bromodeoxyuridine was markedly enhanced when FGF-C(1211) was injected intravenously into carbon tetrachloride-administered mice. Because FGF-C(1211) is heparin independent and nonantigenic, it has potential for clinical and preclinical applications.
Imamura
T
T
Cell Biology Laboratory, National Institute of Bioscience and Human Technology, Ibaraki, Japan.
Tanahashi
T
T
D000818:Animals; D001769:Blood; D001973:Bromodeoxyuridine; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
D007328:Insulin; D008934:Mitogens; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D006493:Heparin; D002251:Carbon Tetrachloride; D001973:Bromodeoxyuridine