Heparin as an inducer of hepatocyte growth factor.
Hepatocyte growth factor (HGF) has mitogenic and unique morphoregulatory functions, and is considered to act as a hepatotrophic and a renotrophic factor for regeneration of the liver and kidney subjected to various insults. We have now obtained evidence that heparin is a potent inducer of HGF production. The addition of heparin to a culture of MRC-5 human embryonic lung fibroblasts increased the HGF concentration in the conditioned medium, in a dose-dependent manner. The maximal stimulation was obtained at 1 microgram/ml heparin and stimulation was 4-fold compared to control cultures. The rate of HGF synthesis in MRC-5 cells, as measured by pulse-labeling with [35S]methionine, and subsequent immunoprecipitation of HGF from both conditioned medium and a cell lysate, was 3-4-fold stimulated by 1 microgram/ml heparin, whereas heparin apparently had no significant effect on the HGF mRNA level. The stimulatory effect of heparin on HGF production was evident in various types of cells, such as MRC-9, IMR-90, and WI-38 human embryonic lung fibroblasts, human skin fibroblasts, HL-60 human promyelocytic leukemic cells and human umbilical vein endothelial cells. In addition to heparin, heparan sulfate also stimulated HGF production, albeit to a lesser extent than heparin; 1.7-fold stimulation with 2 micrograms/ml heparan sulfate. However, other glycosaminoglycans, such as hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, and keratan polysulfate, had no stimulatory effect on HGF production.(ABSTRACT TRUNCATED AT 250 WORDS)
Matsumoto
K
K
Biomedical Research Center, Osaka University Medical School.
Tajima
H
H
Okazaki
H
H
Nakamura
T
T
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004357:Drug Synergism; D005347:Fibroblasts / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008168:Lung / Q000196:embryology; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006493:Heparin; D006497:Heparan Sulfate; D017228:Hepatocyte Growth Factor; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate