Induction of the urokinase plasminogen activator system by oncostatin M promotes endothelial migration.
Oncostatin M (OSM) is an inflammatory cytokine produced by activated macrophages and T-lymphocytes. We have previously demonstrated that OSM-induced endothelial cell migration, unlike endothelial cell proliferation and spindle formation, is independent of basic fibroblast growth factor expression (Wijelath et al. [1997] J. Cell. Sci. 110:871-879). To better understand the mechanism of OSM-induced endothelial cell migration, this study examined the potential role of the plasminogen activator system in promoting OSM mediated endothelial cell migration. OSM stimulated increased mRNA levels of urokinase-plasminogen activator (uPA) and urokinase-plasminogen activator receptor (uPAR) in a time and dose-dependent manner. Transcriptional run-off and mRNA stability analysis demonstrated that the increase in uPA and uPAR mRNA levels was due to both increased gene transcription and mRNA stability. The increase in mRNA correlated with increased protein levels of both uPA and uPAR. This increase was reflected in elevated levels of membrane-bound plasmin activity. OSM-induced endothelial cell migration was only partially dependent on plasmin activity since incubating endothelial cells without plasminogen or, in the presence of aprotinin, resulted in suppression of endothelial cell migration, indicating that OSM promoted endothelial cell migration through both a plasmin-dependent and -independent mechanism. Our results imply a role for OSM in promoting endothelial cell migration via a plasmin-dependent pathway and a uPAR-mediated pathway. Together, these and other recent studies support a role for OSM in modulating the different phases of angiogenesis.
Strand
K
K
Department of Molecular Biology, Hope Heart Institute and Providence Medical Center, Seattle, Washington 98122, USA.
Murray
J
J
Aziz
S
S
Ishida
A
A
Rahman
S
S
Patel
Y
Y
Cardona
C
C
Hammond
W P
WP
Savidge
G
G
Wijelath
E S
ES
D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D006868:Hydrolysis; D053683:Oncostatin M; D010455:Peptides / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
C508351:OSM protein, human; D010455:Peptides; D012333:RNA, Messenger; D053683:Oncostatin M; D014568:Urokinase-Type Plasminogen Activator