Cortactin activation by FVIIa/tissue factor and PAR2 promotes endothelial cell migration

2011 ◽  
Vol 300 (3) ◽  
pp. R577-R585 ◽  
Author(s):  
Tang Zhu ◽  
Joseph A. Mancini ◽  
Przemyslaw Sapieha ◽  
Chun Yang ◽  
Jean-Sébastien Joyal ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Tissue Factor ◽  
Actin Polymerization ◽  
Coagulation Factors ◽  
Cellular Migration ◽  
Endothelial Cell Migration ◽  
Factor Vii ◽  
Cell Periphery ◽  
Migration Assay

Cellular migration is a complex process that requires the polymerization of actin filaments to drive cellular extension. Smooth muscle and cancer cell migration has been shown to be affected by coagulation factors, notably the factor VII (FVIIa) and tissue factor (TF) complex. The present studies delineated mediators involved with the process of FVIIa/TF-induced cell migration and utilized a simple, precise, and reproducible, migration assay. Both FVIIa and protease-activated receptor-2 (PAR2)-activating peptide, SLIGRL, increased the migration rate of porcine cerebral microvascular endothelial cells (pCMVECs) overexpressing human TF. Ras homolog gene family member A (RhoA) and cortactin were upregulated during the process; expression of HIF, actin polymerization nuclear diaphanous-related formin-1 and -2 (Dia1, and Dia2) were unaffected. Gene silencing by shRNA to PAR2, RhoA, and cortactin attenuated this gene upregulation and migration induced by FVIIa/TF. Utilizing immunocellular localization, we demonstrate that during FVIIa/TF and PAR2 activation, cortactin molecules translocate from the cytoplasm to the cell periphery and assist in lamellipodia formation of pCMVECs. Overall, we demonstrate a novel regulation and role for cortactin in FVIIa/TF-mediated endothelial cell migration that occurs through a PAR2 and RhoA dependent mechanism.

scholarly journals CRIF1 deficiency suppresses endothelial cell migration via upregulation of RhoGDI2

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256646
Author(s):  
Harsha Nagar ◽  
Seonhee Kim ◽  
Ikjun Lee ◽  
Su-Jeong Choi ◽  
Shuyu Piao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Cellular Migration ◽  
Endothelial Cell Migration ◽  
Migration And Invasion ◽  
Mitochondrial Functions

Rho GDP-dissociation inhibitor (RhoGDI), a downregulator of Rho family GTPases, prevents nucleotide exchange and membrane association. It is responsible for the activation of Rho GTPases, which regulate a variety of cellular processes, such as migration. Although RhoGDI2 has been identified as a tumor suppressor gene involved in cellular migration and invasion, little is known about its role in vascular endothelial cell (EC) migration. CR6-interacting factor 1 (CRIF1) is a CR6/GADD45-interacting protein with important mitochondrial functions and regulation of cell growth. We examined the expression of RhoGDI2 in CRIF1-deficient human umbilical vein endothelial cells (HUVECs) and its role in cell migration. Expression of RhoGDI2 was found to be considerably higher in CRIF1-deficient HUVECs along with suppression of cell migration. Moreover, the phosphorylation levels of Akt and CREB were decreased in CRIF1-silenced cells. The Akt-CREB signaling pathway was implicated in the changes in endothelial cell migration caused by CRIF1 downregulation. In addition to RhoGDI2, we identified another factor that promotes migration and invasion of ECs. Adrenomedullin2 (ADM2) is an autocrine/paracrine factor that regulates vascular tone and other vascular functions. Endogenous ADM2 levels were elevated in CRIF1-silenced HUVECs with no effect on cell migration. However, siRNA-mediated depletion of RhoGDI2 or exogenous ADM2 administration significantly restored cell migration via the Akt-CREB signaling pathway. In conclusion, RhoGDI2 and ADM2 play important roles in the migration of CRIF1-deficient endothelial cells.

Tissue factor pathway inhibitor (TFPI) interferes with endothelial cell migration by inhibition of both the Erk pathway and focal adhesion proteins

2008 ◽  
Vol 99 (03) ◽  
pp. 576-585 ◽  
Author(s):  
Mathieu Provençal ◽  
Marisol Michaud ◽  
Édith Beaulieu ◽  
David Ratel ◽  
Georges-Étienne Rivard ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Tissue Factor ◽  
Focal Adhesion ◽  
Tissue Factor Pathway Inhibitor ◽  
Endothelial Cell Migration ◽  
Cell Functions ◽  
Tissue Factor Pathway

SummaryTissue factor pathway inhibitor (TFPI) is a plasma Kunitz-type serine protease inhibitor that is mainly known for its inhibition of tissue factor-mediated coagulation. In addition to its anticoagulant properties, emerging data show that TFPI may also regulate endothelial cell functions via a non-haemostatic pathway. In this work we demonstrate that at concentrations within the physiological range,TFPI inhibits both endothelial cell migration and their differentiation into capillary-like structures in vitro. These effects were specific to endothelial cells since no inhibitory effect was observed on the migration of tumor (glio- blastoma) cells. Inhibition of endothelial cell migration was correlated with a concomitant loss in cell adhesion,suggesting an alteration of focal adhesion complex integrity. Accordingly,we observed thatTFPI inhibited the phosphorylation of focal adhesion kinase and paxillin,two key proteins involved in the scaffolding of these complexes, and that this effect was specific to endothelial cells. These results suggest that TFPI influences the angiogenic process via a non-haemostatic pathway, by downregulating the migratory mechanisms of endothelial cells.

scholarly journals Spatial Coordination of Actin Polymerization and ILK–Akt2 Activity during Endothelial Cell Migration

2009 ◽  
Vol 16 (5) ◽  
pp. 661-674 ◽  
Author(s):  
Yi Fan ◽  
Yanqing Gong ◽  
Prabar K. Ghosh ◽  
Linda M. Graham ◽  
Paul L. Fox
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Actin Polymerization ◽  
Endothelial Cell Migration ◽  
Spatial Coordination

scholarly journals Evaluation of a high-throughput in vitro endothelial cell migration assay for the assessment of nicotine and tobacco delivery products

2020 ◽  
Vol 334 ◽  
pp. 110-116
Author(s):  
Emma Bishop ◽  
Damien Breheny ◽  
Katherine Hewitt ◽  
Mark Taylor ◽  
Tomasz Jaunky ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
High Throughput ◽  
Endothelial Cell Migration ◽  
Cell Migration Assay ◽  
Migration Assay

scholarly journals Urokinase-type plasminogen activator is induced in migrating capillary endothelial cells.

1987 ◽  
Vol 105 (6) ◽  
pp. 2535-2541 ◽  
Author(s):  
M S Pepper ◽  
J D Vassalli ◽  
R Montesano ◽  
L Orci
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Plasminogen Activator ◽  
Cellular Migration ◽  
Endothelial Cell Migration ◽  
Vascular Lesions ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

Cellular migration is an essential component of invasive biological processes, many of which have been correlated with an increase in plasminogen activator production. Endothelial cell migration occurs in vivo during repair of vascular lesions and angiogenesis, and can be induced in vitro by wounding a confluent monolayer of cells. By combining the wounded monolayer model with a substrate overlay technique, we show that cells migrating from the edges of an experimental wound display an increase in urokinase-type plasminogen activator (uPA) activity, and that this activity reverts to background levels upon cessation of movement, when the wound has closed. Our results demonstrate a direct temporal relationship between endothelial cell migration and uPA activity, and suggest that induction of uPA activity is a component of the migratory process.

scholarly journals A Quantitative High-Throughput Endothelial Cell Migration Assay

2004 ◽  
Vol 9 (8) ◽  
pp. 712-718 ◽  
Author(s):  
Vladimir Mastyugin ◽  
Elizabeth McWhinnie ◽  
Mark Labow ◽  
Frank Buxton
Keyword(s):  
Cell Migration ◽  
Growth Factors ◽  
Endothelial Cell ◽  
Growth Factor ◽  
High Throughput ◽  
Chemical Compounds ◽  
Endothelial Cell Migration ◽  
Inhibitory Effects ◽  
Migration Assay ◽  
Sensitive Method

By combining the use of BD Biosciences Fluoro Blok ™ membrane-based Boyden chambers with the Cellomics HCS Array Scan, a more sensitive method formeasuring cellmigration has been developed. This assay is based on counting nuclei ofmigrated cells on the bottomof the filter rather than conventional approaches, which usemeasurement of totalwell fluorescence. This cellmigration assay provides approximately 10-fold increased signal/background compared to conventional approaches and can be used to assess the effects of growth factors on endothelial cell migration and to screen chemical compounds for inhibitory effects on growth factor–mediated endothelial cell migration.

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