Inhibition of urokinase synthesis and cell surface binding alters the motile behavior of embryonic endocardial-derived mesenchymal cells in vitro.
The expression of the serine protease urokinase is elevated during the epithelial-mesenchymal transformation of the endocardium in the developing avian heart. Elevated urokinase expression is associated with the migrating mesenchymal cells of the atrioventricular canal and bulbotruncus and not the myocardium. Treatment of isolated endocardial-derived mesenchymal cells with phosphatidyinositol-specific phospholipase C released urokinase and its receptor from the cell surface and caused significant alterations in cell morphology and motility. Likewise inhibition of urokinase synthesis by treatment of cells with antisense oligonucleotides also inhibited the migration and motility of the endocardial-derived cells. These results suggest an important role for this enzyme in cell-matrix interactions and cell migration during development.
McGuire
P G
PG
Department of Anatomy, University of New Mexico School of Medicine, Albuquerque 87131.
Alexander
S M
SM
D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003370:Coturnix / Q000196:embryology; D004699:Endocardium / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009924:Organ Culture Techniques; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D055293:Receptors, Urokinase Plasminogen Activator; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013499:Surface Properties; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D009124:Muscle Proteins; D016376:Oligonucleotides, Antisense; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D015842:Serine Proteinase Inhibitors; D010727:Phosphoric Diester Hydrolases; D014568:Urokinase-Type Plasminogen Activator; D043265:Phosphatidylinositol Diacylglycerol-Lyase