scholarly journals Kakonein restores diabetes‐induced endothelial junction dysfunction via promoting autophagy‐mediated NLRP 3 inflammasome degradation

2021 ◽  
Author(s):  
Dawei Lian ◽  
Jiaying Liu ◽  
Ruifang Han ◽  
Jiaqi Jin ◽  
Li Zhu ◽  
...  
Keyword(s):  
Endothelial Junction

scholarly journals Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin

2015 ◽  
Vol 212 (13) ◽  
pp. 2267-2287 ◽  
Author(s):  
Maike Frye ◽  
Martina Dierkes ◽  
Verena Küppers ◽  
Matthias Vockel ◽  
Janina Tomm ◽  
...  
Keyword(s):  
Tyrosine Phosphatase ◽  
Endothelial Barrier ◽  
Vascular Endothelial ◽  
Leukocyte Transmigration ◽  
Gene Ablation ◽  
Nonmuscle Myosin Ii ◽  
Endothelial Junctions ◽  
The Stability ◽  
Endothelial Junction

Vascular endothelial (VE)–protein tyrosine phosphatase (PTP) associates with VE-cadherin, thereby supporting its adhesive activity and endothelial junction integrity. VE-PTP also associates with Tie-2, dampening the tyrosine kinase activity of this receptor that can support stabilization of endothelial junctions. Here, we have analyzed how interference with VE-PTP affects the stability of endothelial junctions in vivo. Blocking VE-PTP by antibodies, a specific pharmacological inhibitor (AKB-9778), and gene ablation counteracted vascular leak induction by inflammatory mediators. In addition, leukocyte transmigration through the endothelial barrier was attenuated. Interference with Tie-2 expression in vivo reversed junction-stabilizing effects of AKB-9778 into junction-destabilizing effects. Furthermore, lack of Tie-2 was sufficient to weaken the vessel barrier. Mechanistically, inhibition of VE-PTP stabilized endothelial junctions via Tie-2, which triggered activation of Rap1, which then caused the dissolution of radial stress fibers via Rac1 and suppression of nonmuscle myosin II. Remarkably, VE-cadherin gene ablation did not abolish the junction-stabilizing effect of the VE-PTP inhibitor. Collectively, we conclude that inhibition of VE-PTP stabilizes challenged endothelial junctions in vivo via Tie-2 by a VE-cadherin–independent mechanism. In the absence of Tie-2, however, VE-PTP inhibition destabilizes endothelial barrier integrity in agreement with the VE-cadherin–supportive effect of VE-PTP.

The CellBorderTracker, a novel tool to quantitatively analyze spatiotemporal endothelial junction dynamics at the subcellular level

2015 ◽  
Vol 144 (6) ◽  
pp. 517-532 ◽  
Author(s):  
Jochen Seebach ◽  
Abdallah Abu Taha ◽  
Janine Lenk ◽  
Nico Lindemann ◽  
Xiaoyi Jiang ◽  
...  
Keyword(s):  
Endothelial Junction ◽  
Subcellular Level

scholarly journals Desert Hedgehog-driven endothelium integrity is enhanced by Gas1 but negatively regulated by Cdon

2020 ◽  
Author(s):  
Candice Chapouly ◽  
Pierre-Louis Hollier ◽  
Sarah Guimbal ◽  
Lauriane Cornuault ◽  
Alain-Pierre Gadeau ◽  
...  
Keyword(s):  
Brain Cortex ◽  
Molecular Level ◽  
Negative Regulator ◽  
The Past ◽  
Inflammatory Conditions ◽  
Downstream Effector ◽  
Desert Hedgehog ◽  
Vessel Integrity ◽  
Endothelial Junction ◽  
The Brain

AbstractEvidences accumulated within the past decades, identified Hedgehog (Hh) signaling as a new regulator of micro-vessel integrity. More specifically, we recently identified Desert Hedgehog (Dhh) as a downstream effector of Klf2 in endothelial cells (ECs).ObjectiveThe purpose of this study is to investigate whether Hh co-receptors Gas1 and Cdon may be used as therapeutic targets to modulate Dhh signaling in ECs.Methods and resultsWe demonstrated that both Gas1 and Cdon are expressed in adult ECs and relied on either siRNAs or EC specific conditional KO mice to investigate their role. We found that Gas1 deficiency mainly photocopies Dhh deficiency especially by inducing VCAM-1 and ICAM-1 overexpression while Cdon deficiency has opposite effects by promoting endothelial junction integrity. At a molecular level, Cdon prevents Dhh binding to Ptch1 and thus acts a decoy receptor for Dhh, while Gas1 promotes Dhh binding to Smo and as a result potentiates Dhh effects. Since Cdon is overexpressed in ECs treated by inflammatory cytokines including TNFα and Il1β, we then tested whether Cdon inhibition would promote endothelium integrity in acute inflammatory conditions and found that both fibrinogen and IgG extravasation were decreased in association with an increased Cdh5 expression in the brain cortex of EC specific Cdon KO mice administered locally with Il1β.ConclusionAltogether these results demonstrate that Gas1 is a positive regulator of Dhh in ECs while Cdon is a negative regulator. Interestingly Cdon blocking molecules may then be used to promote endothelium integrity at least in inflammatory conditions.

scholarly journals Altered expressions of endothelial junction protein of placental capillaries in premature infants with intraventricular hemorrhage

2016 ◽  
Vol 25 (3) ◽  
pp. 143-50 ◽  
Author(s):  
Maria Ekawati ◽  
Ninik Mujihartini ◽  
Ahmad A. Jusuf ◽  
Nani Dharmasetiawani ◽  
Sri W.A. Jusman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Premature Infants ◽  
Intraventricular Hemorrhage ◽  
Tissue Response ◽  
Cranial Ultrasound ◽  
Cross Sectional ◽  
Altered Expression ◽  
Hypoxia Group ◽  
Junction Protein ◽  
Endothelial Junction

Background: Placental hypoxia may lead to oxidative stress, which inflicts damage to capillary protein junction. The aim of this study was to evaluate altered expression of endothelial junction protein of capillaries in hypoxia condition and to observe its correlation with the incidence of  intraventricular hemorrhage in premature infants.Methods: A cross-sectional study was conducted by using placental tissues of premature infants as amodel of capillary integrity (29 hypoxic and 29 non-hypoxic). Hypoxia inducible factor (HIF)-1α was measured to define placental tissue response to hypoxia; malondialdehyde (MDA) and glutathione (GSH) served as markers of oxidative stress. The expressions of junctional proteins, N-cadherin and occludin were analyzed by immunohistochemistry. Intraventricular hemorrhage (IVH) was detected by cranial ultrasound at the third day. Unpaired t test, Mann-Whitney, and Chi-square tests were used to analyze the data.Results: The HIF-1α and MDA levels were slightly, but not significantly, higher in hypoxia group {13.64±8.70 pg/mg protein and 10.31 pmol/mg tissue (ranged 1.92–93.61), respectively}  compared to non- hypoxia group {10.65±5.35 pg/mg protein and 9.77 pmol/mg tissue (ranged 2.42–93.31)}. GSH levels were not different in both groups (38.14 (ranged 9.44–118.91) and  38.47(ranged 16.49–126.76) ng/mg protein, respectively. mRNA expression of N-cadherin (0.13) and occludin (0.096) were significantly lower in hypoxia comparedto non-hypoxia group (p=0,001), while protein expression of  N-cadherin (3.4; 75.9; 6.9; 13.8%) and occludin  (20.7; 3.4; 69.0; 3.4; 6.9%)  in hypoxia group was not associated with IVH (p=0.783 and p=0.743).Conclusion: Hypoxia altered expression of endothelial junction protein in placental capillaries, but no association with intraventricular hemorrhage was observed.

scholarly journals A Critical Role for Phosphatidylinositol (3,4,5)-Trisphosphate–Dependent Rac Exchanger 1 in Endothelial Junction Disruption and Vascular Hyperpermeability

2012 ◽  
Vol 111 (12) ◽  
pp. 1517-1527 ◽  
Author(s):  
Ram P. Naikawadi ◽  
Ni Cheng ◽  
Stephen M. Vogel ◽  
Feng Qian ◽  
Dianqing Wu ◽  
...  
Keyword(s):  
Critical Role ◽  
Endothelial Junction

Perturbation of endothelial junction proteins by Staphylococcus aureus α-toxin: inhibition of endothelial gap formation by adrenomedullin

2006 ◽  
Vol 126 (3) ◽  
pp. 305-316 ◽  
Author(s):  
Andreas C. Hocke ◽  
Bettina Temmesfeld-Wollbrueck ◽  
Bernd Schmeck ◽  
Katharina Berger ◽  
Eckehard M. Frisch ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gap Formation ◽  
Endothelial Junction ◽  
Toxin Inhibition ◽  
Junction Proteins

Identification of CD146 as a component of the endothelial junction involved in the control of cell-cell cohesion

Blood ◽  
2001 ◽  
Vol 98 (13) ◽  
pp. 3677-3684 ◽  
Author(s):  
Nathalie Bardin ◽  
Francine Anfosso ◽  
Jean-Marc Massé ◽  
Elisabeth Cramer ◽  
Florence Sabatier ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Umbilical Vein ◽  
Cell Surface Expression ◽  
Cell Junction ◽  
Immunoglobulin Superfamily ◽  
Cell Surface Molecule ◽  
Apical Side ◽  
Endothelial Junction ◽  
Cell Cell

Abstract CD146 is a cell-surface molecule belonging to the immunoglobulin superfamily and expressed in all types of human endothelial cells. Confocal and electron microscopic analysis of confluent human umbilical vein endothelial cells (HUVECs) were used to demonstrate that CD146 is a component of the endothelial junction. Double immunolabeling with vascular endothelial cadherin showed that CD146 is localized outside the adherens junction. Moreover, CD146 expression is not restricted to the junction, since part of the labeling was detectable at the apical side of the HUVECs. Interestingly, cell-surface expression of CD146 increased when HUVECs reached confluence. In addition, the paracellular permeability of CD146-transfected fibroblast cells was decreased compared with that of control cells. Finally, CD146 colocalized with actin, was partly resistant to Triton X-100 extraction, and had its expression altered by actin-disrupting agents, indicating that CD146 is associated with the actin cytoskeleton. These results show the regulated expression of CD146 at areas of cell-cell junction and strongly suggest involvement of CD146 as a mediator of cell-cell interaction.

scholarly journals Rasip1 regulates vertebrate vascular endothelial junction stability through Epac1-Rap1 signaling

Blood ◽  
2013 ◽  
Vol 122 (22) ◽  
pp. 3678-3690 ◽  
Author(s):  
Christopher W. Wilson ◽  
Leon H. Parker ◽  
Christopher J. Hall ◽  
Tanya Smyczek ◽  
Judy Mak ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Vascular Endothelial ◽  
Key Points ◽  
Endothelial Junction

Key Points RASIP1 is required for stabilizing nascent patent blood vessels in both mice and zebrafish. RASIP1 is a dynamic effector of EPAC1-RAP1 signaling that controls actin bundling and restricts junction remodeling in vitro and in vivo.

Intermedin restricts vessel sprouting by inhibiting the loosening of endothelial junction

2015 ◽  
Vol 458 (1) ◽  
pp. 174-179 ◽  
Author(s):  
Fei Xiao ◽  
Li-jun Wang ◽  
Huan Zhao ◽  
Chun Tan ◽  
De-nian Wang ◽  
...  
Keyword(s):  
Endothelial Junction

Interferon-γ and Interleukin-10 Reciprocally Regulate Endothelial Junction Integrity and Barrier Function,

2001 ◽  
Vol 61 (3) ◽  
pp. 291 ◽  
Author(s):  
Tadayuki Oshima ◽  
F.Stephen Laroux ◽  
Laura L. Coe ◽  
Zenichi Morise ◽  
Shigeyuki Kawachi ◽  
...  
Keyword(s):  
Barrier Function ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Endothelial Junction
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