Monocyte-expressed urokinase inhibits vascular smooth muscle cell growth by activating Stat1.
After vascular injury, a remodeling process occurs that features leukocyte migration and infiltration. Loss of endothelial integrity allows the leukocytes to interact with vascular smooth muscle cells (VSMCs) and to elicit "marching orders"; however, the signaling processes are poorly understood. We found that human monocytes inhibit VSMC proliferation and induce a migratory potential. The monocytes signal the VSMCs through the urokinase-type plasminogen activator (uPA). The VSMC uPA receptor (uPAR) receives the signal and activates the transcription factor Stat1 that, in turn, mediates the antiproliferative effects. These results provide the first evidence that monocytes signal VSMCs by mechanisms involving the fibrinolytic system, and they imply an important link between the uPA/uPAR-related signaling machinery and human vascular disease.
Kunigal
Sateesh
S
Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.
Kusch
Angelika
A
Tkachuk
Natalia
N
Tkachuk
Sergey
S
Jerke
Uwe
U
Haller
Hermann
H
Dumler
Inna
I
D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014568:Urokinase-Type Plasminogen Activator / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D007371:Interferon-gamma; D014568:Urokinase-Type Plasminogen Activator