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Monocyte-expressed urokinase inhibits vascular smooth muscle cell growth by activating Stat1

Item Type:Article
Title:Monocyte-expressed urokinase inhibits vascular smooth muscle cell growth by activating Stat1
Creators Name:Kunigal, S. and Kusch, A. and Tkachuk, N. and Tkachuk, S. and Jerke, U. and Haller, H. and Dumler, I.
Abstract: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.
Keywords:Cell Division, Cell Movement, Cell Surface Receptors, Coculture Techniques, Cultured Cells, DNA-Binding Proteins, Genetic Transcription, Interferon-{gamma}, Knockout Mice, STAT1 Transcription Factor, Signal Transduction, Trans-Activators, Transgenic Mice, Urokinase Plasminogen Activator Receptors, Urokinase-Type Plasminogen Activator, Vascular Smooth Muscle, Animals, Mice
Publisher:American Society of Hematology
Page Range:4377-4383
Date:15 December 2003
Official Publication:https://doi.org/10.1182/blood-2002-12-3872
PubMed:View item in PubMed

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