Roles of VE-Cadherin in Hypoxia Induced Injury of Pulmonary Microvascular Endothelial Barrier

Background: Hypoxia induced injury of pulmonary microvascular endothelial barrier is closely related to the pathogenesis of acute lung injury after lung transplantation. VE-cadherin is an important structural molecule for pulmonary microvascular endothelial barrier. In this study, we aim to investigate the roles of VE-cadherin in hypoxia induced injury of pulmonary microvascular endothelial barrier. Methods: Rat model of hypoxia and cultured pulmonary microvascular endothelial cells (PMVECs) were utilized. Determination of PMVECs apoptosis, skeleton combination was conducted to verify the effects of hypoxia on injury of pulmonary microvascular endothelial barrier. In addition, VE-cadherin expression was modulated by administration of siRNA in order to investigate the roles of VE-cadherin in hypoxia induced PMVECs apoptosis and skeleton recombination. Results: Our data indicated that expression of VE-cadherin was down-regulated in hypoxia-exposed PMVECs. Whereas, in the cells treated using siRNA, down-regulation of VE-cadherin did not trigger PMVECs apoptosis, but it increased the sensitivity of PMVECs to the hypoxia induced apoptosis. In cases of hypoxia, the expression of VE-cadherin was significantly down-regulated, together with endothelial skeleton recombination and increase of permeability, which then triggered endothelial barrier dysfunction. Conclusions: These data verify that VE-cadherin expression played an important role in hypoxia induced PMVECs apoptosis and cellular skeletal recombination.

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Inhibition of microRNA-92a ameliorates lipopolysaccharide-induced endothelial barrier dysfunction by targeting ITGA5 through the PI3K/Akt signaling pathway in human pulmonary microvascular endothelial cells

International Immunopharmacology ◽

10.1016/j.intimp.2019.106060 ◽

2020 ◽

Vol 78 ◽

pp. 106060 ◽

Cited By ~ 1

Author(s):

Fan Xu ◽

Fachun Zhou

Keyword(s):

Endothelial Cells ◽

Signaling Pathway ◽

Akt Signaling ◽

Endothelial Barrier ◽

Microvascular Endothelial Cells ◽

Akt Signaling Pathway ◽

Barrier Dysfunction ◽

Pulmonary Microvascular Endothelial Cells ◽

Endothelial Barrier Dysfunction ◽

Microvascular Endothelial

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The HSP90 Inhibitor, AUY-922, Protects and Repairs Human Lung Microvascular Endothelial Cells from Hydrochloric Acid-Induced Endothelial Barrier Dysfunction

Cells ◽

10.3390/cells10061489 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1489

Author(s):

Ruben M. L. Colunga Biancatelli ◽

Pavel Solopov ◽

Betsy Gregory ◽

John D. Catravas

Keyword(s):

Endothelial Cells ◽

Hydrochloric Acid ◽

Human Lung ◽

Hsp90 Inhibitor ◽

Endothelial Barrier ◽

Microvascular Endothelial Cells ◽

Dependent Manner ◽

Barrier Dysfunction ◽

Endothelial Barrier Dysfunction ◽

Microvascular Endothelial

Exposure to hydrochloric acid (HCl) leads acutely to asthma-like symptoms, acute respiratory distress syndrome (ARDS), including compromised alveolo-capillary barrier, and respiratory failure. To better understand the direct effects of HCl on pulmonary endothelial function, we studied the characteristics of HCl-induced endothelial barrier dysfunction in primary cultures of human lung microvascular endothelial cells (HLMVEC), defined the involved molecular pathways, and tested the potentially beneficial effects of Heat Shock Protein 90 (HSP90) inhibitors. HCl impaired barrier function in a time- and concentration-dependent manner and was associated with activation of Protein Kinase B (AKT), Ras homolog family member A (RhoA) and myosin light chain 2 (MLC2), as well as loss of plasmalemmal VE-cadherin, rearrangement of cortical actin, and appearance of inter-endothelial gaps. Pre-treatment or post-treatment of HLMVEC with AUY-922, a third-generation HSP90 inhibitor, prevented and restored HCl-induced endothelial barrier dysfunction. AUY-922 increased the expression of HSP70 and inhibited the activation (phosphorylation) of extracellular-signal regulated kinase (ERK) and AKT. AUY-922 also prevented the HCl-induced activation of RhoA and MLC2 and the internalization of plasmalemmal VE-cadherin. We conclude that, by increasing the expression of cytoprotective proteins, interfering with actomyosin contractility, and enhancing the expression of junction proteins, inhibition of HSP90 may represent a useful approach for the management of HCl-induced endothelial dysfunction and acute lung injury.

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Unfractionated heparin ameliorates pulmonary microvascular endothelial barrier dysfunction via microtubule stabilization in acute lung injury

Respiratory Research ◽

10.1186/s12931-018-0925-6 ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 7

Author(s):

Shengtian Mu ◽

Yina Liu ◽

Jing Jiang ◽

Renyu Ding ◽

Xu Li ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Unfractionated Heparin ◽

Endothelial Barrier ◽

Barrier Dysfunction ◽

Microtubule Stabilization ◽

Endothelial Barrier Dysfunction ◽

Microvascular Endothelial

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Tissue Inhibitor of Metalloproteinase-2 Regulates Matrix Metalloproteinase-2–Mediated Endothelial Barrier Dysfunction and Breast Cancer Cell Transmigration through Lung Microvascular Endothelial Cells

Molecular Cancer Research ◽

10.1158/1541-7786.mcr-09-0523 ◽

2010 ◽

Vol 8 (7) ◽

pp. 939-951 ◽

Cited By ~ 5

Author(s):

Qiang Shen ◽

Eugene S. Lee ◽

Robert L. Pitts ◽

Mack H. Wu ◽

Sarah Y. Yuan

Keyword(s):

Breast Cancer ◽

Endothelial Cells ◽

Matrix Metalloproteinase ◽

Breast Cancer Cell ◽

Tissue Inhibitor Of Metalloproteinase ◽

Endothelial Barrier ◽

Matrix Metalloproteinase 2 ◽

Microvascular Endothelial Cells ◽

Barrier Dysfunction ◽

Endothelial Barrier Dysfunction

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ASK1-p38 cascaded signal mediates pulmonary microvascular endothelial barrier injury induced by the return of PHSML in rats

RSC Advances ◽

10.1039/c8ra08473d ◽

2019 ◽

Vol 9 (9) ◽

pp. 4870-4875

Author(s):

Muhammad Fawad ◽

Muhammad Abbas ◽

Limin Zhang ◽

Yuping Zhang ◽

Yaxiong Guo

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Hemorrhagic Shock ◽

Endothelial Barrier ◽

Vascular Endothelial ◽

Barrier Dysfunction ◽

Endothelial Barrier Dysfunction ◽

Mesenteric Lymph ◽

Microvascular Endothelial

The return of post-hemorrhagic shock mesenteric lymph (PHSML) induces pulmonary vascular endothelial barrier dysfunction, which results in acute lung injury.

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