scholarly journals Membrane Type 1-Matrix Metalloproteinase Is Activated during Migration of Human Endothelial Cells and Modulates Endothelial Motility and Matrix Remodeling

2001 ◽  
Vol 276 (40) ◽  
pp. 37491-37500 ◽  
Author(s):  
Beatriz G. Gálvez ◽  
Salomón Matı́as-Román ◽  
Juan P. Albar ◽  
Francisco Sánchez-Madrid ◽  
Alicia G. Arroyo
Keyword(s):  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Matrix Remodeling ◽  
Human Endothelial Cells ◽  
Membrane Type

scholarly journals Caveolae Are a Novel Pathway for Membrane-Type 1 Matrix Metalloproteinase Traffic in Human Endothelial Cells

2004 ◽  
Vol 15 (2) ◽  
pp. 678-687 ◽  
Author(s):  
Beatriz G. Gálvez ◽  
Salomón Matías-Román ◽  
María Yáñez-Mó ◽  
Miguel Vicente-Manzanares ◽  
Francisco Sánchez-Madrid ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Endocytic Pathway ◽  
Αvβ3 Integrin ◽  
Human Endothelial Cells ◽  
Caveolin 1 ◽  
Selective Targeting ◽  
Membrane Type ◽  
And Function

The extracellular matrix (ECM) distinctly modulates membrane type 1-matrix metalloproteinase (MT1-MMP) in human endothelial cells (ECs). Herein, ECM-dependent RhoA activation is shown to regulate MT1-MMP localization and activity as well as clathrin-independent internalization in confluent ECs. In this regard, caveolae are revealed as the major MT1-MMP endocytic pathway in human ECs. Thus, MT1-MMP is present at caveolae with caveolin-1 and both proteins together with αvβ3 integrin colocalize at endothelial motility-associated extensions. Remarkably, caveolae traffic is required for proper MT1-MMP localization, activity, and function in migratory ECs as demonstrated by both treatment with caveolae-disrupting agents or selective targeting caveolin-1 expression by interference RNA. Thus, caveolae-mediated traffic constitutes a novel mechanism for MT1-MMP regulation in ECs during angiogenesis.

Cdc42 and RhoA have opposing roles in regulating membrane type 1-matrix metalloproteinase localization and matrix metalloproteinase-2 activation

2008 ◽  
Vol 295 (3) ◽  
pp. C600-C610 ◽  
Author(s):  
Eric Ispanovic ◽  
Damiano Serio ◽  
Tara L. Haas
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Matrix Metalloproteinase ◽  
Actin Cytoskeleton ◽  
Cortical Actin ◽  
Rhoa Activity ◽  
Surface Localization ◽  
Cell Surface Localization ◽  
Membrane Type

Proteolysis of the basement membrane and interstitial matrix occurs early in the angiogenic process and requires matrix metalloproteinase (MMP) activity. Skeletal muscle microvascular endothelial cells exhibit robust actin stress fibers, low levels of membrane type 1 (MT1)-MMP expression, and minimal MMP-2 activation. Depolymerization of the actin cytoskeleton increases MT1-MMP expression and MMP-2 activation. Rho family GTPases are regulators of actin cytoskeleton dynamics, and their activity can be modulated in response to angiogenic stimuli such as vascular endothelial growth factor (VEGF). Therefore, we investigated their roles in MMP-2 and MT1-MMP production. Endothelial cells treated with H1152 [an inhibitor of Rho kinase (ROCK)] induced stress fiber depolymerization and an increase in cortical actin. Both MMP-2 and MT1-MMP mRNA increased, which translated into greater MMP-2 protein production and activation. ROCK inhibition rapidly increased cell surface localization of MT1-MMP and increased PI3K activity, which was required for MMP-2 activation. Constitutively active Cdc42 increased cortical actin polymerization, phosphatidylinositol 3-kinase activity, MT1-MMP cell surface localization, and MMP-2 activation similarly to inhibition of ROCK. Activation of Cdc42 was sufficient to decrease RhoA activity. Capillary sprout formation in a three-dimensional collagen matrix was increased in cultures treated with RhoAN19 or Cdc42QL and, conversely, decreased in cultures treated with dominant negative Cdc42N17. VEGF stimulation also induced activation of Cdc42 while inhibiting RhoA activity. Furthermore, VEGF-dependent activation of MMP-2 was reduced by inhibition of Cdc42. These results suggest that Cdc42 and RhoA have opposing roles in regulating cell surface localization of MT1-MMP and MMP-2 activation.

scholarly journals Membrane type 1–matrix metalloproteinase is involved in migration of human monocytes and is regulated through their interaction with fibronectin or endothelium

Blood ◽  
2005 ◽  
Vol 105 (10) ◽  
pp. 3956-3964 ◽  
Author(s):  
Salomón Matías-Román ◽  
Beatriz G. Gálvez ◽  
Laura Genís ◽  
María Yáñez-Mó ◽  
Gonzalo de la Rosa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Human Monocytes ◽  
Tumor Cell Migration ◽  
Monocyte Migration ◽  
Tnf Α ◽  
Membrane Type

Abstract Membrane type 1–matrix metalloproteinase (MT1-MMP) is involved in endothelial and tumor-cell migration, but its putative role in leukocyte migration has not been characterized yet. Here, we demonstrate that anti–MT1-MMP monoclonal antibody (mAb) impaired monocyte chemotactic protein-1 (MCP-1)–stimulated monocyte migration on fibronectin (FN), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). In addition, monocyte transmigration through tumor necrosis factor-α (TNF-α)–activated endothelium is also inhibited by anti–MT1-MMP mAb. Therefore, regulation of MT1-MMP in human peripheral blood monocytes was investigated. First, MT1-MMP clustering was observed at motility-associated membrane protrusions of MCP-1–stimulated monocytes migrating on FN, VCAM-1, or ICAM-1 and at the leading edge, together with profilin, of monocytes transmigrating through activated endothelial cells. In addition, up-regulation of MT1-MMP expression was induced in human monocytes upon attachment to FN in a manner dependent on α4β1 and α5β1 integrins. Binding of monocytes to TNF-α–activated human endothelial cells as well as to VCAM-1 or ICAM-1 also resulted in an increase of MT1-MMP expression. These findings correlated with an enhancement of MT1-MMP fibrinolytic activity in monocytes bound to FN, VCAM-1, or ICAM-1. Our data show that MT1-MMP is required during human monocyte migration and endothelial transmigration and that MT1-MMP localization, expression, and activity are regulated in monocytes upon contact with FN or endothelial ligands, pointing to a key role of MT1-MMP in monocyte recruitment during inflammation.

scholarly journals ECM regulates MT1-MMP localization with β1 or αvβ3 integrins at distinct cell compartments modulating its internalization and activity on human endothelial cells

2002 ◽  
Vol 159 (3) ◽  
pp. 509-521 ◽  
Author(s):  
Beatriz G. Gálvez ◽  
Salomón Matías-Román ◽  
María Yáñez-Mó ◽  
Francisco Sánchez-Madrid ◽  
Alicia G. Arroyo
Keyword(s):  
Endothelial Cells ◽  
Αvβ3 Integrin ◽  
Human Endothelial Cells ◽  
Distinct Cell ◽  
Intercellular Contacts ◽  
Αvβ3 Integrins ◽  
Membrane Type ◽  
And Function ◽  
Cellular Compartments

Regulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) by different extracellular matrices (ECMs) on human endothelial cells (ECs) has been investigated. First, MT1-MMP is found at the intercellular contacts of confluent ECs grown on β1 integrin–dependent matrix such as type 1 collagen (COL I), fibronectin (FN), or fibrinogen (FG), but not on gelatin (GEL) or vitronectin (VN). The novel localization of MT1-MMP at cell–cell contacts is assessed by confocal videomicroscopy of MT1-MMP-GFP–transfected ECs. Moreover, MT1-MMP colocalizes with β1 integrins at the intercellular contacts, whereas it is preferentially found with αvβ3 integrin at motility-associated structures on migrating ECs. In addition, clustered integrins recruit MT1-MMP and neutralizing anti-β1 or anti-αv integrin mAb displace MT1-MMP from its specific sites, pointing to a biochemical association that is finally demonstrated by coimmunoprecipitation assays. On the other hand, COL I, FN, or FG up-regulate cell surface MT1-MMP on confluent ECs by an impairment of its internalization, whereas expression and internalization are not modified on GEL or VN. In addition, MT1-MMP activity is diminished in confluent ECs on COL I, FN, or FG. Finally, MT1-MMP participates and cooperates with β1 and αvβ3 integrins in the migration of ECs on different ECM. These data show a novel mechanism by which ECM regulates MT1-MMP association with β1 or αvβ3 integrins at distinct cellular compartments, thus modulating its internalization, activity, and function on human ECs.

scholarly journals Sphingosine-1-phosphate induces the association of membrane-type 1 matrix metalloproteinase with p130Cas in endothelial cells

FEBS Letters ◽  
2007 ◽  
Vol 582 (3) ◽  
pp. 399-404 ◽  
Author(s):  
Denis Gingras ◽  
Marisol Michaud ◽  
Geneviève Di Tomasso ◽  
Eric Béliveau ◽  
Carine Nyalendo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Sphingosine 1 Phosphate ◽  
Membrane Type

scholarly journals Membrane Type 1–Matrix Metalloproteinase/Akt Signaling Axis Modulates TNF-α-Induced Procoagulant Activity and Apoptosis in Endothelial Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e105697 ◽  
Author(s):  
Hiroshi Ohkawara ◽  
Toshiyuki Ishibashi ◽  
Koichi Sugimoto ◽  
Kazuhiko Ikeda ◽  
Kazuei Ogawa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Akt Signaling ◽  
Procoagulant Activity ◽  
Tnf Α ◽  
Signaling Axis ◽  
Membrane Type

scholarly journals Functional interplay between endothelial nitric oxide synthase and membrane type 1–matrix metalloproteinase in migrating endothelial cells

Blood ◽  
2007 ◽  
Vol 110 (8) ◽  
pp. 2916-2923 ◽  
Author(s):  
Laura Genís ◽  
Pilar Gonzalo ◽  
Antonio S. Tutor ◽  
Beatriz G. Gálvez ◽  
Antonio Martínez-Ruiz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Molecular Mechanisms ◽  
Type I Collagen ◽  
Tube Formation ◽  
Type I ◽  
Endothelial Migration ◽  
Membrane Type

Abstract Nitric oxide (NO) is essential for vascular homeostasis and is also a critical modulator of angiogenesis; however, the molecular mechanisms of NO action during angiogenesis remain elusive. We have investigated the potential relationship between NO and membrane type 1–matrix metalloproteinase (MT1-MMP) during endothelial migration and capillary tube formation. Endothelial NO synthase (eNOS) colocalizes with MT1-MMP at motility-associated structures in migratory human endothelial cells (ECs); moreover, NO is produced at these structures and is released into the medium during EC migration. We have therefore addressed 2 questions: (1) the putative regulation of MT1-MMP by NO in migratory ECs; and (2) the requirement for MT1-MMP in NO-induced EC migration and tube formation. NO upregulates MT1-MMP membrane clustering on migratory human ECs, and this is accompanied by increased degradation of type I collagen substrate. MT1-MMP membrane expression and localization are impaired in lung ECs from eNOS-deficient mice, and these cells also show impaired migration and tube formation in vitro. Inhibition of MT1-MMP with a neutralizing antibody impairs NOinduced tube formation by human ECs, and NO-induced endothelial migration and tube formation are impaired in lung ECs from mice deficient in MT1-MMP. MT1-MMP thus appears to be a key molecular effector of NO during the EC migration and angiogenic processes, and is a potential therapeutic target for NO-associated vascular disorders.

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