scholarly journals PECAM-1 regulates proangiogenic properties of endothelial cells through modulation of cell-cell and cell-matrix interactions

2010 ◽  
Vol 299 (6) ◽  
pp. C1468-C1484 ◽  
Author(s):  
SunYoung Park ◽  
Terri A. DiMaio ◽  
Elizabeth A. Scheef ◽  
Christine M. Sorenson ◽  
Nader Sheibani
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Immunoglobulin Superfamily ◽  
Capillary Morphogenesis ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions ◽  
Cell Cell

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a member of the immunoglobulin superfamily of cell adhesion molecules with important roles in angiogenesis and inflammation. However, the molecular and cellular mechanisms, and the role that specific PECAM-1 isoforms play in these processes, remain elusive. We recently showed attenuation of retinal vascular development and neovascularization in PECAM-1-deficient (PECAM-1−/−) mice. To gain further insight into the role of PECAM-1 in these processes, we isolated primary retinal endothelial cells (EC) from wild-type (PECAM-1+/+) and PECAM-1−/− mice. Lack of PECAM-1 had a significant impact on endothelial cell-cell and cell-matrix interactions, resulting in attenuation of cell migration and capillary morphogenesis. Mechanistically these changes were associated with a significant decrease in expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability in PECAM-1−/− retinal EC. PECAM-1−/− retinal EC also exhibited a lower rate of apoptosis under basal and challenged conditions, consistent with their increased growth rate. Furthermore, reexpression of PECAM-1 was sufficient to restore migration and capillary morphogenesis of null cells in an isoform-specific manner. Thus PECAM-1 expression modulates proangiogenic properties of EC, and these activities are significantly influenced by alternative splicing of its cytoplasmic domain.

scholarly journals Induction of Caspase-Mediated Cell Death by Matrix Metalloproteinases in Cerebral Endothelial Cells after Hypoxia—Reoxygenation

2004 ◽  
Vol 24 (7) ◽  
pp. 720-727 ◽  
Author(s):  
Sun-Ryung Lee ◽  
Eng H. Lo
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Matrix Metalloproteinases ◽  
Caspase 3 ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Endothelial Cell Death ◽  
Cell Matrix Interactions ◽  
Hypoxia Reoxygenation

Matrix metalloproteinases (MMPs) may contribute to the pathophysiology of cerebral ischemia by degrading matrix components in the neurovascular unit. In this study, the authors document a pathway by which MMPs interfere with cell—matrix interactions and trigger caspase-mediated cytotoxicity in brain endothelial cells. Hypoxia—reoxygenation induced endothelial cytotoxicity. Cytoprotection with zDEVD-fmk confirmed that cell death was partly caspase mediated. The temporal profile of caspase-3 activation was matched by elevations in MMP-2 and MMP-9. MMP inhibitors significantly decreased caspase-3 activation and reduced endothelial cell death. Degradation of matrix fibronectin confirmed the presence of extracellular proteolysis. Increasing integrin-linked kinase signaling with the β1 integrin-activating antibody (8A2) ameliorated endothelial cytotoxicity. The results suggest that MMP-9 and MMP-2 contribute to caspase-mediated brain endothelial cell death after hypoxia—reoxygenation by disrupting cell—matrix interactions and homeostatic integrin signaling.

scholarly journals A 109-amino-acid C-terminal fragment of Alzheimer's-disease amyloid precursor protein contains a sequence, -RHDS-, that promotes cell adhesion

1992 ◽  
Vol 288 (3) ◽  
pp. 1053-1059 ◽  
Author(s):  
J Ghiso ◽  
A Rostagno ◽  
J E Gardella ◽  
L Liem ◽  
P D Gorevic ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Adhesion ◽  
Amino Acid ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Cell Matrix ◽  
Terminal Fragment ◽  
Matrix Interactions ◽  
Cell Matrix Interactions ◽  
Cell Cell

Amyloid beta (A beta), the major constituent of the fibrils composing senile plaques and vascular amyloid deposits in Alzheimer's disease (AD) and related disorders, is a 39-42-residue self-aggregating degradation peptide of a larger multidomain membrane glycoprotein designated amyloid precursor protein (APP). An array of biological functions has been assigned to different APP domains, including growth regulation, neurotoxicity, inhibitory activity of serine proteinases and promotion of cell-cell and cell-matrix interactions. A beta is generated through an as-yet-unknown catabolic pathway that by-passes or inhibits the cleavage of APP within the A beta sequence. We have identified a 16 kDa intermediate APP C-terminal fragment containing A beta in leptomeningeal vessels of aged normal individuals and AD patients by means of its immunoreactivity with a panel of four different anti-(APP C-terminal) antibodies, indicating a different pathway of APP processing. Previous studies have indicated that the APP C-terminal domain is the most likely to be involved in cell-matrix interactions. A 109-amino-acid construct C109 with a sequence analogous to the C-terminal of APP (positions 587-695 of APP695), similar in length and immunoreactivity to the 16 kDa fragment, was found to promote cell adhesion. By use of synthetic peptides, this activity was initially located to the extracellular 28 residues of A beta. Inhibition studies demonstrated that the sequence RHDS (amino acids 5-8 of A beta, corresponding to residues 601-604 of APP695 was responsible for the adhesion-promoting activity. The interaction is dependent on bivalent cations and can be blocked either by the tetrapeptides RHDS and RGDS or by an anti-(beta 1 integrin) antibody. Thus, through integrin-like surface receptors, APP or its derivative proteolytic fragments containing the sequence RHDS may modulate cell-cell or cell-matrix interactions.

Reactive oxygen species mediate Rac-induced loss of cell-cell adhesion in primary human endothelial cells

2002 ◽  
Vol 115 (9) ◽  
pp. 1837-1846 ◽  
Author(s):  
Sandra van Wetering ◽  
Jaap D. van Buul ◽  
Safira Quik ◽  
Frederik P. J. Mul ◽  
Eloise C. Anthony ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Reactive Oxygen ◽  
Small Gtpases ◽  
Endothelial Cell Migration ◽  
Oxygen Species ◽  
Cell Cell

The integrity of the endothelium is dependent on cell-cell adhesion, which is mediated by vascular-endothelial (VE)-cadherin. Proper VE-cadherin-mediated homotypic adhesion is, in turn, dependent on the connection between VE-cadherin and the cortical actin cytoskeleton. Rho-like small GTPases are key molecular switches that control cytoskeletal dynamics and cadherin function in epithelial as well as endothelial cells. We show here that a cell-penetrating, constitutively active form of Rac (Tat-RacV12) induces a rapid loss of VE-cadherin-mediated cell-cell adhesion in endothelial cells from primary human umbilical veins (pHUVEC). This effect is accompanied by the formation of actin stress fibers and is dependent on Rho activity. However,transduction of pHUVEC with Tat-RhoV14, which induces pronounced stress fiber and focal adhesion formation, did not result in a redistribution of VE-cadherin or an overall loss of cell-cell adhesion. In line with this observation, endothelial permeability was more efficiently increased by Tat-RacV12 than by Tat-RhoV14. The loss of cell-cell adhesion, which is induced by Tat-RacV12, occurred in parallel to and was dependent upon the intracellular production of reactive oxygen species (ROS). Moreover, Tat-RacV12 induced an increase in tyrosine phosphorylation of a component the VE-cadherin-catenin complex, which was identified as α-catenin. The functional relevance of this signaling pathway was further underscored by the observation that endothelial cell migration, which requires a transient reduction of cell-cell adhesion, was blocked when signaling through ROS was inhibited. In conclusion, Rac-mediated production of ROS represents a previously unrecognized means of regulating VE-cadherin function and may play an important role in the (patho)physiology associated with inflammation and endothelial damage as well as with endothelial cell migration and angiogenesis.

Intestinal transformation results in transforming growth factor-beta-dependent alteration in tumor cell-cell matrix interactions

Surgery ◽  
2003 ◽  
Vol 133 (5) ◽  
pp. 568-579 ◽  
Author(s):  
David H. Berger ◽  
Christine A. O'Mahony ◽  
Hongmiao Sheng ◽  
Jinyi Shao ◽  
Daniel Albo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Growth Factor Beta ◽  
Cell Matrix Interactions ◽  
Cell Cell

scholarly journals A co-culture device with a tunable stiffness to understand combinatorial cell–cell and cell–matrix interactions

2013 ◽  
Vol 5 (11) ◽  
pp. 1344 ◽  
Author(s):  
Nikhil Rao ◽  
Gregory N. Grover ◽  
Ludovic G. Vincent ◽  
Samantha C. Evans ◽  
Yu Suk Choi ◽  
...  
Keyword(s):  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions ◽  
Tunable Stiffness ◽  
Cell Cell

Effects of collagenase-cleavage of type I collagen on alpha2beta1 integrin-mediated cell adhesion

1998 ◽  
Vol 111 (8) ◽  
pp. 1127-1135 ◽  
Author(s):  
A.J. Messent ◽  
D.S. Tuckwell ◽  
V. Knauper ◽  
M.J. Humphries ◽  
G. Murphy ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Type I Collagen ◽  
Cell Attachment ◽  
Heat Denaturation ◽  
Type I ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Triple Helices ◽  
Collagen Fragment ◽  
Cell Matrix Interactions

In this paper we show that collagenase-3 cleavage of type I collagen has a marked effect on alpha2beta1 integrin-mediated interactions with the collagen fragments generated. Isolated alpha2beta1 integrin and alpha2 integrin A-domain were found to bind to both native collagen and native 3/4 fragment and, to a lesser degree, native 1/4 fragment. Whole integrin and integrin A-domain binding were lost after heat denaturation of the collagen fragments. At physiological temperature, cell adhesion to triple-helical 3/4 fragment via alpha2beta1 integrin was still possible; however, no alpha2beta1 integrin-mediated adhesion to the 1/4 fragment was observed. Unwinding of the collagen fragment triple helices by heating to physiological temperatures prior to adsorption to plastic tissue culture plates resulted in total abrogation of HT1080 cell attachment to either fragment. These results provide significant evidence in support of a role for matrix-metalloproteinase cleavage of the extracellular matrix in modifying cell-matrix interactions.

Sign in / Sign up

Export Citation Format

Share Document