Heparin‐hepatocyte growth factor complex with low plasma clearance and retained hepatocyte proliferating activity

@article{Kato1994HeparinhepatocyteGF,
  title={Heparin‐hepatocyte growth factor complex with low plasma clearance and retained hepatocyte proliferating activity},
  author={Yoshihisa Kato and K. X. Liu and Toshifumi Nakamura and Yuichi Sugiyama},
  journal={Hepatology},
  year={1994},
  volume={20}
}
Because hepatocyte growth factor is known to have affinity for heparin, we studied the binding isotherm and found that hepatocyte growth factor has a high‐affinity binding site for 35S‐heparin with an equilibrium dissociation constant of approximately 0.6 nmol/L. We then analyzed the pharmacokinetic behavior of the heparin–hepatocyte growth factor complex in rats. The area under the plasma concentration‐time profiles of trichloroacetic acid–precipitable radioactivities from 0 to 30 min after… Expand
Existence of two nonlinear elimination mechanisms for hepatocyte growth factor in rats.
TLDR
The results suggest that heparin mainly inhibits low-affinity HGF uptake by complexing with HGF, whereas its effect on RME is relatively minor. Expand
Existence of two nonlinear elimination mechanisms for hepatocyte growth factor in rats.
TLDR
The results suggest that heparin mainly inhibits low-affinity HGF uptake by complexing with HGF, whereas its effect on RME is relatively minor. Expand
Ligand-induced downregulation of receptor-mediated clearance of hepatocyte growth factor in rats.
TLDR
Downregulation could also be observed for HGF receptor density in isolated liver plasma membrane, assessed by Western blot analysis by means of anti-receptor antibody, 30 min after injection of excess unlabeled HGF, supporting the hypothesis that the overall elimination of HGF from the systemic circulation can be affected by a change in HGF receptors density on the liver cell surface. Expand
Hepatocyte growth factor in serum after injection of unfractionated and low molecular weight heparin in healthy individuals
TLDR
UH was more potent in inducing HGF increase than LMWH, both after a single injection and after several days of treatment, and the rise in bioactive HGF after heparin treatment was stable during continued treatment. Expand
Protamine enhances the proliferative activity of hepatocyte growth factor in rats.
TLDR
The enhancing effect of protamine on HGF-induced liver regeneration results from dual effects exerted by protamine 1) lowering the overall elimination of HGF and 2) directly stimulating hepatocyte mitosis induced by HGF. Expand
Protamine enhances the proliferative activity of hepatocyte growth factor in rats.
TLDR
The enhancing effect of protamine on HGF-induced liver regeneration results from dual effects exerted by protamine 1) lowering the overall elimination of HGF and 2) directly stimulating hepatocyte mitosis induced by HGF. Expand
Activation of hepatocyte growth factor/activin A/follistatin system during hemodialysis: role of heparin.
TLDR
HGF/activin A/follistatin system is activated and disturbed in chronic hemodialysis patients, including depletion of tissue stores of activin A. Expand
A Novel Drug Delivery System of Hepatocyte Growth Factor (HGF): Utilization of Heparin-HGF Complex
Although hepatocyte growth factor (HGF) is most potent mitogen for mature hepatocytes and expected to be developed as a treatment for a liver diseases, its plasma residence time is very short, andExpand
Characterization of the Enhancing Effect of Protamine on the Proliferative Activity of Hepatocyte Growth Factor in Rat Hepatocytes
TLDR
The enhancing effect of protamine on the mitogenic activity of HGF on hepatocytes requires pretreatment with protamine for a short period presumably required for its binding to cell-surface heparin, implying possible regulation of c-met autophosphorylation by HSPG. Expand
A mutant of deleted variant of hepatocyte growth factor (dHGF) with alanine substitution in the N-terminal basic region has higher activity in vivo.
TLDR
Analysis of in vivo hepatotropic and renotropic activities of #2 and its distribution to target tissues, liver and kidney suggests that #2 is more potent than dHGF as a hepatotropic factor in vivo. Expand
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References

SHOWING 1-10 OF 36 REFERENCES
Decrease in the hepatic clearance of hepatocyte growth factor in carbon tetrachloride–intoxicated rats
TLDR
The finding that the cell‐surface hepatocyte growth factor receptors are greatly down‐regulated in carbon tetrachloride–intoxicated rats, suggests that the hepatic clearance of hepatocytes growth factor through receptor‐mediated endocytosis decreases in carbonTetrach chloroacetic acid–precipitable rats. Expand
Identification and partial characterization of receptor binding sites for HGF on rat hepatocytes.
TLDR
The data show that HGF exerts its biological effect on hepatocytes (stimulation of DNA synthesis) through a specific and unique cell-surface receptor. Expand
Identification and change in the receptor for hepatocyte growth factor in rat liver after partial hepatectomy or induced hepatitis.
TLDR
It is proposed that HGF which can be immediately supplied to the liver after hepatic injury will function as a trigger for regeneration of this organ. Expand
Purification and subunit structure of hepatocyte growth factor from rat platelets
TLDR
Biological and chemical properties showed that HGF was not identical with any known growth factors, including platelet‐derived growth factor (PDGF), which was found to be a beat‐ and acid‐labile protein that was inactivated by reduction with dithiothreitol. Expand
Tissue distribution of hepatocyte growth factor receptor and its exclusive down-regulation in a regenerating organ after injury.
TLDR
The presence of control mechanisms governing HGF receptor function only in a regenerating organ after injury is suggested, suggesting that HGF may be a multifunctional growth factor, targeting to a variety of organs, and not restricted to liver. Expand
Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure.
TLDR
HGF stimulates proliferation of cultured hepatocytes more effectively than human epidermal growth factor (hEGF) or insulin, and the effect of hHGF is additive or synergistic with the maximal effects of hEGF and insulin. Expand
Purification and characterization of hepatocyte growth factor from injured liver of carbon tetrachloride-treated rats.
TLDR
The findings indicate that the HGF-like factor in damaged liver of CCl4-treated rats is HGF and that liver itself can produce HGF when injured. Expand
Receptor-mediated endocytosis of epidermal growth factor by hepatocytes in the perfused rat liver: ligand and receptor dynamics
TLDR
Results suggest that EGF receptors are internalized and that their rate of recycling to the surface from intracellular sites is governed by the rate of entry of ligand and/or receptor into lysosomes. Expand
Molecular cloning and expression of human hepatocyte growth factor
TLDR
The nucleotide sequence of the human HGF cDNA reveals that both α- andβ-chains are contained in a single open reading frame coding for a pre-pro precursor protein of 728 amino acids, which indicates that the activity of HGF is not species-specific. Expand
Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and has a potent antihepatitis effect in vivo
TLDR
It is shown that intravenously injected hepatocyte growth factor stimulates the growth of hepatocytes in mouse liver and protects the integrity of hepatocyte in vivo against hepatitis caused by hepatotoxin, and may prove to be useful as a treatment for liver diseases. Expand
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