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  • Title: Heparin as an inducer of hepatocyte growth factor.
    Author: Matsumoto K, Tajima H, Okazaki H, Nakamura T.
    Journal: J Biochem; 1993 Dec; 114(6):820-6. PubMed ID: 8138538.
    Abstract:
    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)
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