Hepatocyte growth factor enhances MMP activity in human endothelial cells.
Scatter factor (SF) or hepatocyte growth factor (HGF) has been identified as an angiogenic factor. Angiogenesis requires not only tube formation but also invasion of pericytes and extracellular matrix (ECM) remodeling to promote new vessel stabilization. In the current study, the effect of SF/HGF on endothelial cell (EC) production of matrix metalloproteinases (MMPs) was explored. We showed that SF/HGF enhanced MT1-MMP synthesis and induced MMP-2 activation in two human EC lines: dermal microvessel EC and coronary arterial EC. Furthermore, SF/HGF accelerated EC invasion into matrix, an activity that could be inhibited by a MMP inhibitor. We also demonstrated that the MAP kinase cascade is critical in signal transduction pathway from SF/HGF stimulation to MT1-MMP up-regulation. The current study indicates that MMP activation is a novel effect of SF/HGF on ECs.
Wang
H
H
Cardiovascular Therapeutics, Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105, USA. He.WANG@wl.com
Keiser
J A
JA
D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003331:Coronary Vessels / Q000166:cytology; D020405:Dermis / Q000098:blood supply; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008970:Molecular Weight; D010766:Phosphorylation / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D004338:Drug Combinations; D005419:Flavonoids; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D011509:Proteoglycans; D012333:RNA, Messenger; C059485:matrigel; D017228:Hepatocyte Growth Factor; D003094:Collagen; D019859:Proto-Oncogene Proteins c-met; D020928:Mitogen-Activated Protein Kinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one