scholarly journals Effects of indoxyl sulfate on adherens junctions of endothelial cells and the underlying signaling mechanism

2012 ◽  
Vol 113 (3) ◽  
pp. 1034-1043 ◽  
Author(s):  
Yu-Sen Peng ◽  
Yen-Tung Lin ◽  
Ying Chen ◽  
Kuan-Yu Hung ◽  
Seu-Mei Wang
Keyword(s):  
Endothelial Cells ◽  
Adherens Junctions ◽  
Indoxyl Sulfate ◽  
Signaling Mechanism

scholarly journals Spatial and temporal relationships between cadherins and PECAM-1 in cell-cell junctions of human endothelial cells.

1994 ◽  
Vol 126 (1) ◽  
pp. 247-258 ◽  
Author(s):  
O Ayalon ◽  
H Sabanai ◽  
M G Lampugnani ◽  
E Dejana ◽  
B Geiger
Keyword(s):  
Endothelial Cells ◽  
Plasma Membrane ◽  
Vascular System ◽  
Adherens Junctions ◽  
Microscopic Analysis ◽  
Membrane Receptors ◽  
Temporal Organization ◽  
Cell Junctions ◽  
Short Treatment ◽  
Cell Cell

The integrity of the endothelial layer, which lines the entire cavity of the vascular system, depends on tight adhesion of the cells to the underlying basement membrane as well as to each other. It has been previously shown that such interactions occur via membrane receptors that determine the specificity, topology, and mechanical properties of the surface adhesion. Cell-cell junctions between endothelial cells, in culture and in situ, involve both Ca(2+)-dependent and -independent mechanisms that are mediated by distinct adhesion molecules. Ca(2+)-dependent cell-cell adhesion occurs mostly via members of the cadherin family, which locally anchor the microfilament system to the plasma membrane, in adherens junctions. Ca(2+)-independent adhesions were reported to mainly involve members of the Ig superfamily. In this study, we performed three-dimensional microscopic analysis of the relative subcellular distributions of these two endothelial intercellular adhesion systems. We show that cadherins are located at adjacent (usually more apical), yet clearly distinct domains of the lateral plasma membrane, compared to PECAM-1. Moreover, cadherins were first organized in adherens junctions within 2 h after seeding of endothelial cells, forming multiple lateral patches which developed into an extensive belt-like structure over a period of 24 h. PECAM-1 became associated with surface adhesions significantly later and became progressively associated with the cadherin-containing adhesions. Cadherins and PECAM-1 also differed in their detergent extractability, reflecting differences in their mode of association with the cytoskeleton. Moreover, the two adhesion systems could be differentially modulated since short treatment with the Ca2+ chelator EGTA, disrupted the cadherin junctions leaving PECAM-1 apparently intact. These results confirm that endothelial cells possess distinct intercellular contact mechanisms that differ in their spatial and temporal organization as well as in their functional properties.

scholarly journals Circulating extracellular vesicles from patients with acute chest syndrome disrupt adherens junctions between endothelial cells

2020 ◽  
Author(s):  
Gabrielle Lapping-Carr ◽  
Joanna Gemel ◽  
Yifan Mao ◽  
Gianna Sparks ◽  
Margaret Harrington ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Extracellular Vesicles ◽  
Adherens Junctions ◽  
Acute Chest Syndrome

Mechanotransduction by integrin is essential for IL-6 secretion from endothelial cells in response to uniaxial continuous stretch

2005 ◽  
Vol 288 (5) ◽  
pp. C1012-C1022 ◽  
Author(s):  
Akitoshi Sasamoto ◽  
Masato Nagino ◽  
Satoshi Kobayashi ◽  
Keiji Naruse ◽  
Yuji Nimura ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Kinase Inhibitor ◽  
Umbilical Vein ◽  
Nuclear Factor Κb ◽  
Inhibitory Peptide ◽  
Signaling Mechanism ◽  
Iκb Kinase ◽  
Intracellular Ca ◽  
Protein Kinase C Inhibitor ◽  
Umbilical Vein Endothelial Cells

We previously reported that uniaxial continuous stretch in human umbilical vein endothelial cells (HUVECs) induced interleukin-6 (IL-6) secretion via IκB kinase (IKK)/nuclear factor-κB (NF-κB) activation. The aim of the present study was to clarify the upstream signaling mechanism responsible for this phenomenon. Stretch-induced IKK activation and IL-6 secretion were inhibited by application of α5β1 integrin-inhibitory peptide (GRGDNP), phosphatidylinositol 3-kinase inhibitor (LY-294002), phospholipase C-γ inhibitor (U-73122), or protein kinase C inhibitor (H7). Although depletion of intra- or extracellular Ca2 + pool using thapsigargin (TG) or EGTA, respectively, showed little effect, a TG-EGTA mixture significantly inhibited stretch-induced IKK activation and IL-6 secretion. An increase in the intracellular Ca2 + concentration ([Ca2 +]i) upon continuous stretch was observed even in the presence of TG, EGTA, or GRGDNP, but not in a solution containing the TG-EGTA mixture, indicating that both integrin activation and [Ca2 +]i rise are crucial factors for stretch-induced IKK activation and after IL-6 secretion in HUVECs. Furthermore, while PKC activity was inhibited by the TG-EGTA mixture, GRGDNP, LY-294002, or U-73122, PLC-γ activity was retarded by GRGDNP or LY-294002. These results indicate that continuous stretch-induced IL-6 secretion in HUVECs depends on outside-in signaling via integrins followed by a PI3-K-PLC-γ-PKC-IKK-NF-κB signaling cascade. Another crucial factor, [Ca2 +]i increase, may at least be required to activate PKC needed for NF-κB activation.

scholarly journals Structure of artificial and natural VE-cadherinbased adherens junctions

2008 ◽  
Vol 36 (2) ◽  
pp. 189-193 ◽  
Author(s):  
Jean-Christophe Taveau ◽  
Mathilde Dubois ◽  
Olivier Le Bihan ◽  
Sylvain Trépout ◽  
Sébastien Almagro ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Actin Cytoskeleton ◽  
Self Assembly ◽  
Adherens Junctions ◽  
Actin Binding ◽  
Vascular Endothelial ◽  
Vascular Integrity ◽  
Trans Orientation ◽  
Annexin 2

In vascular endothelium, adherens junctions between endothelial cells are composed of VE-cadherin (vascular endothelial cadherin), an adhesive receptor that is crucial for the proper assembly of vascular structures and the maintenance of vascular integrity. As a classical cadherin, VE-cadherin links endothelial cells together by homophilic interactions mediated by its extracellular part and associates intracellularly with the actin cytoskeleton via catenins. Although, from structural crystallographic data, a dimeric structure arranged in a trans orientation has emerged as a potential mechanism of cell–cell adhesion, the cadherin organization within adherens junctions remains controversial. Concerning VE-cadherin, its extracellular part possesses the capacity to self-associate in solution as hexamers consisting of three antiparallel cadherin dimers. VE-cadherin-based adherens junctions were reconstituted in vitro by assembly of a VE-cadherin EC (extracellular repeat) 1–EC4 hexamer at the surfaces of liposomes. The artificial adherens junctions revealed by cryoelectron microscopy appear as a two-dimensional self-assembly of hexameric structures. This cadherin organization is reminiscent of that found in native desmosomal junctions. Further structural studies performed on native VE-cadherin junctions would provide a better understanding of the cadherin organization within adherens junctions. Homophilic interactions between cadherins are strengthened intracellularly by connection to the actin cytoskeleton. Recently, we have discovered that annexin 2, an actin-binding protein connects the VE-cadherin–catenin complex to the actin cytoskeleton. This novel link is labile and promotes the endothelial cell switch from a quiescent to an angiogenic state.

scholarly journals Flow mechanotransduction regulates traction forces, intercellular forces, and adherens junctions

2012 ◽  
Vol 302 (11) ◽  
pp. H2220-H2229 ◽  
Author(s):  
Lucas H. Ting ◽  
Jessica R. Jahn ◽  
Joon I. Jung ◽  
Benjamin R. Shuman ◽  
Shirin Feghhi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Laminar Flow ◽  
Adherens Junctions ◽  
Cell Junctions ◽  
Flow Conditions ◽  
Traction Forces ◽  
Disturbed Flow ◽  
Cytoskeletal Tension ◽  
Static Conditions ◽  
Cell Cell

Endothelial cells respond to fluid shear stress through mechanotransduction responses that affect their cytoskeleton and cell-cell contacts. Here, endothelial cells were grown as monolayers on arrays of microposts and exposed to laminar or disturbed flow to examine the relationship among traction forces, intercellular forces, and cell-cell junctions. Cells under laminar flow had traction forces that were higher than those under static conditions, whereas cells under disturbed flow had lower traction forces. The response in adhesion junction assembly matched closely with changes in traction forces since adherens junctions were larger in size for laminar flow and smaller for disturbed flow. Treating the cells with calyculin-A to increase myosin phosphorylation and traction forces caused an increase in adherens junction size, whereas Y-27362 cause a decrease in their size. Since tugging forces across cell-cell junctions can promote junctional assembly, we developed a novel approach to measure intercellular forces and found that these forces were higher for laminar flow than for static or disturbed flow. The size of adherens junctions and tight junctions matched closely with intercellular forces for these flow conditions. These results indicate that laminar flow can increase cytoskeletal tension while disturbed flow decreases cytoskeletal tension. Consequently, we found that changes in cytoskeletal tension in response to shear flow conditions can affect intercellular tension, which in turn regulates the assembly of cell-cell junctions.

MP032ROLE OF CREB1 IN THE REGULATION OF EXPRESSION OF OAT1 AND OAT3 BY HUMAN ENDOTHELIAL CELLS IN THE PRESENCE OF PROTEIN BOUND UREMIC TOXINS p-CRESYL SULFATE AND INDOXYL SULFATE

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii439-iii439
Author(s):  
Regiane Cunha ◽  
Giane Favretto ◽  
Paulo Gregório ◽  
Rayana Marciel ◽  
Valentina Busato ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Human Endothelial Cells ◽  
Regulation Of Expression

17 β‐estradiol transiently disrupts adherens junctions in endothelial cells

2005 ◽  
Vol 19 (10) ◽  
pp. 1368-1370 ◽  
Author(s):  
Tanja Groten ◽  
Amy A. Pierce ◽  
Arthur C. Huen ◽  
H. William Schnaper
Keyword(s):  
Endothelial Cells ◽  
Adherens Junctions

scholarly journals Pathogenic Hantaviruses Andes Virus and Hantaan Virus Induce Adherens Junction Disassembly by Directing Vascular Endothelial Cadherin Internalization in Human Endothelial Cells

2010 ◽  
Vol 84 (14) ◽  
pp. 7405-7411 ◽  
Author(s):  
Elena Gorbunova ◽  
Irina N. Gavrilovskaya ◽  
Erich R. Mackow
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Adherens Junctions ◽  
Paracellular Permeability ◽  
Cell Permeability ◽  
Hantaan Virus ◽  
Vascular Endothelial ◽  
Vascular Endothelial Cadherin ◽  
Andes Virus ◽  
Endothelial Cell Permeability

ABSTRACT Hantaviruses infect endothelial cells and cause 2 vascular permeability-based diseases. Pathogenic hantaviruses enhance the permeability of endothelial cells in response to vascular endothelial growth factor (VEGF). However, the mechanism by which hantaviruses hyperpermeabilize endothelial cells has not been defined. The paracellular permeability of endothelial cells is uniquely determined by the homophilic assembly of vascular endothelial cadherin (VE-cadherin) within adherens junctions, which is regulated by VEGF receptor-2 (VEGFR2) responses. Here, we investigated VEGFR2 phosphorylation and the internalization of VE-cadherin within endothelial cells infected by pathogenic Andes virus (ANDV) and Hantaan virus (HTNV) and nonpathogenic Tula virus (TULV) hantaviruses. We found that VEGF addition to ANDV- and HTNV-infected endothelial cells results in the hyperphosphorylation of VEGFR2, while TULV infection failed to increase VEGFR2 phosphorylation. Concomitant with the VEGFR2 hyperphosphorylation, VE-cadherin was internalized to intracellular vesicles within ANDV- or HTNV-, but not TULV-, infected endothelial cells. Addition of angiopoietin-1 (Ang-1) or sphingosine-1-phosphate (S1P) to ANDV- or HTNV-infected cells blocked VE-cadherin internalization in response to VEGF. These findings are consistent with the ability of Ang-1 and S1P to inhibit hantavirus-induced endothelial cell permeability. Our results suggest that pathogenic hantaviruses disrupt fluid barrier properties of endothelial cell adherens junctions by enhancing VEGFR2-VE-cadherin pathway responses which increase paracellular permeability. These results provide a pathway-specific mechanism for the enhanced permeability of hantavirus-infected endothelial cells and suggest that stabilizing VE-cadherin within adherens junctions is a primary target for regulating endothelial cell permeability during pathogenic hantavirus infection.

ETS-Related Gene Activation Preserves Adherens Junctions and Permeability in Microvascular Endothelial Cells

Shock ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Binu Tharakan ◽  
Felicia A. Hunter ◽  
Saravanakumar Muthusamy ◽  
Sonya Randolph ◽  
Crystal Byrd ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adherens Junctions ◽  
Gene Activation ◽  
Microvascular Endothelial Cells ◽  
Related Gene ◽  
Microvascular Endothelial
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