Role of formic receptors in soluble urokinase receptor-induced human vascular smooth muscle migration

The Journal of Surgical Research
Enrico A DuruMark G Davies

Abstract

Vascular smooth muscle cell (VSMC) migration in response to urokinase is dependent on binding of the urokinase molecule to the urokinase plasminogen receptor (uPAR) and cleavage of the receptor. The aim of this study was to examine the role of the soluble uPAR (suPAR) in VSMC migration. Human VSMCs were cultured in vitro. Linear wound and Boyden microchemotaxis assays of migration were performed in the presence of suPAR. Inhibitors to G-protein signaling and kinase activation were used to study these pathways. Assays were performed for mitogen-activated protein kinase and epidermal growth factor receptor activation. suPAR induced concentration-dependent migration of VSMC, which was G protein-dependent and was blocked by Gαi and Gβγ inhibitors. Removal of the full uPAR molecule by incubation of the cells with a phospholipase did not interfere with this response. suPAR induced ERK1/2, p38(MAPK), and c-Jun N-terminal kinase [JNK] activation in a Gαi/Gβγ-dependent manner, and interruption of these signaling pathways prevented suPAR-mediated migration. suPAR activity was independent of plasmin activity. suPAR did not activate epidermal growth factor receptor. Interruption of the low affinity N-formyl-Met-Leu-Phe receptor (FPRL1) but...Continue Reading

References

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Feb 8, 2005·Journal of Vascular Surgery·William J TanskiMark G Davies
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Jul 23, 2008·Perspectives in Vascular Surgery and Endovascular Therapy·Kimon Bekelis, Nicos Labropoulos
Dec 23, 2008·The Journal of Surgical Research·Yiping ZouMark G Davies

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Citations

May 2, 2017·Frontiers in Physiology·Francesca DonadoniVanessa Díaz-Zuccarini
Feb 3, 2019·International Journal of Molecular Sciences·Yosuke Kanno
Jun 25, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Eun Young Kim, Stuart E Dryer
Jul 16, 2021·The Journal of Clinical Investigation·Ke Zhu, Jochen Reiser

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