Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth.
Hepatocyte Growth Factor (HGF, also known as Scatter Factor) is a powerful mitogen or motility factor in different cells, acting through the tyrosine kinase receptor encoded by the MET protooncogene. Endothelial cells express the MET gene and expose at the cell surface the mature protein (p190MET) made of a 50 kD (alpha) subunit disulfide linked to a 145-kD (beta) subunit. HGF binding to endothelial cells identifies two sites with different affinities. The higher affinity binding site (Kd = 0.35 nM) corresponds to the p190MET receptor. Sub-nanomolar concentrations of HGF, but not of a recombinant inactive precursor, stimulate the receptor kinase activity, cell proliferation and motility. HGF induces repairs of a wound in endothelial cell monolayer. HGF stimulates the scatter of endothelial cells grown on three-dimensional collagen gels, inducing an elongated phenotype. In the rabbit cornea, highly purified HGF promotes neovascularization at sub-nanomolar concentrations. HGF lacks activities related to hemostasis-thrombosis, inflammation and endothelial cells accessory functions. These data show that HGF is an in vivo potent angiogenic factor and in vitro induces endothelial cells to proliferate and migrate.
Bussolino
F
F
Department of Genetics, Biology and Medical Chemistry, University of Torino.
Di Renzo
M F
MF
Ziche
M
M
Bocchietto
E
E
Olivero
M
M
Naldini
L
L
Gaudino
G
G
Tamagnone
L
L
Coffer
A
A
Comoglio
P M
PM
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009389:Neovascularization, Pathologic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met; D011519:Proto-Oncogenes; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014471:Umbilical Veins; D014945:Wound Healing / Q000187:drug effects*
D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D011505:Protein-Tyrosine Kinases; D019859:Proto-Oncogene Proteins c-met