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Mini Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell Dev. Biol. | doi: 10.3389/fcell.2019.00280

Differential regulation of LPS-mediated VE-cadherin disruption in human endothelial cells and the underlying signaling pathways: A mini review

 Yee Han Chan1, 2, 3, Hanis Hazeera Harith1, 2, 3,  Daud A. Israf Ali1, 2, 3 and  Chau Ling Tham1, 2, 3*
  • 1Putra Malaysia University, Malaysia
  • 2Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia
  • 3Independent researcher, Malaysia

Endothelial cells lining the inner vascular wall form a monolayer that contributes to the selective permeability of endothelial barrier. This selective permeability is mainly regulated by an endothelium-specific adherens junctional protein, known as vascular endothelial-cadherin (VE-cadherin). In endothelial cells, the adherens junction comprises of VE-cadherin and its associated adhesion molecules such as p120, α-catenin and β-catenin, in which α-catenin links cytoplasmic tails of VE-cadherin to actin cytoskeleton through β-catenin. Proinflammatory stimuli such as lipopolysaccharide (LPS) are capable of attenuating vascular integrity through the disruption of VE-cadherin adhesion in endothelial cells. To date, numerous studies demonstrated the disruption of adherens junction as a result of phosphorylation-mediated VE-cadherin disruption. However, the outcomes from these studies were inconsistent and non-conclusive as different cell fractions were used to examine the effect of LPS on the disruption of VE-cadherin. By using Western Blot, some studies utilized total protein lysate and reported decreased protein expression while some studies reported unchanged expression. Other studies which used membrane and cytosolic fractions of protein extract demonstrated decreased and increased VE-cadherin expression, respectively. Despite the irregularities, the results of immunofluorescence staining are consistent with the formation of intercellular gap. Besides that, the overall underlying disruptive mechanisms of VE-cadherin remain largely unknown. Therefore, this mini review will focus on cell fractions used in different studies with different human endothelial cell models, and relate them to the results obtained in Western Blot and immunofluorescence staining in order to give some insights into the overall mechanisms of LPS-induced VE-cadherin disruption and address the discrepancy in VE-cadherin expression.

Keywords: VE-cadherin, adherens junction, lipopolysaccharide, Endothelial hyperpermeability, Tyrosine phosphorylation, internalization

Received: 30 Jul 2019; Accepted: 31 Oct 2019.

Copyright: © 2019 Chan, Harith, Israf Ali and Tham. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Chau Ling Tham, Putra Malaysia University, Selangor Darul Ehsan, Malaysia,