Next Article in Journal
Interaction of Clostridium perfringens Iota Toxin and Lipolysis-Stimulated Lipoprotein Receptor (LSR)
Next Article in Special Issue
Urea Memory: Transient Cell Exposure to Urea Causes Persistent Mitochondrial ROS Production and Endothelial Dysfunction
Previous Article in Journal
Association of Uremic Toxins and Inflammatory Markers with Physical Performance in Dialysis Patients
Previous Article in Special Issue
The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Toxins 2018, 10(10), 404;

Uremia Impacts VE-Cadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions

Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba 80050-540, Brazil
Cell Biology Department, Universidade Federal do Paraná, Curitiba 80050-540, Brazil
Basic Pathology Department, Universidade Federal do Paraná, Curitiba 80050-540, Brazil
Division of Nephrology, Ambroise Paré University Hospital, APHP, Boulogne-Billancourt, 92100 Paris, France and Inserm U1018, Team 5, CESP, UVSQ, Paris-Saclay University, 94800 Villejuif, France
Universitè de Picardie Jules Verne, MP3CV and CHU d’Amiens, 80025 Amiens, France
Pontifícia Universidade Católica do Paraná, School of Medicine, Curitiba 80215-901, Brazil
Author to whom correspondence should be addressed.
Received: 2 August 2018 / Revised: 16 September 2018 / Accepted: 29 September 2018 / Published: 7 October 2018
(This article belongs to the Special Issue Uremia and Cardiovascular Disease)
Full-Text   |   PDF [4294 KB, uploaded 7 October 2018]   |  


Endothelial dysfunction in uremia can result in cell-to-cell junction loss and increased permeability, contributing to cardiovascular diseases (CVD) development. This study evaluated the impact of the uremic milieu on endothelial morphology and cell junction’s proteins. We evaluated (i) serum levels of inflammatory biomarkers in a cohort of chronic kidney disease (CKD) patients and the expression of VE-cadherin and Zonula Occludens-1 (ZO-1) junction proteins on endothelial cells (ECs) of arteries removed from CKD patients during renal transplant; (ii) ECs morphology in vitro under different uremic conditions, and (iii) the impact of uremic toxins p-cresyl sulfate (PCS), indoxyl sulfate (IS), and inorganic phosphate (Pi) as well as of total uremic serum on VE-cadherin and ZO-1 gene and protein expression in cultured ECs. We found that the uremic arteries had lost their intact and continuous endothelial morphology, with a reduction in VE-cadherin and ZO-1 expression. In cultured ECs, both VE-cadherin and ZO-1 protein expression decreased, mainly after exposure to Pi and uremic serum groups. VE-cadherin mRNA expression was reduced while ZO-1 was increased after exposure to PCS, IS, Pi, and uremic serum. Our findings show that uremia alters cell-to-cell junctions leading to an increased endothelial damage. This gives a new perspective regarding the pathophysiological role of uremia in intercellular junctions and opens new avenues to improve cardiovascular outcomes in CKD patients. View Full-Text
Keywords: chronic kidney disease; uremic toxins; intercellular junctions chronic kidney disease; uremic toxins; intercellular junctions

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Maciel, R.A.P.; Cunha, R.S.; Busato, V.; Franco, C.R.C.; Gregório, P.C.; Dolenga, C.J.R.; Nakao, L.S.; Massy, Z.A.; Boullier, A.; Pecoits-Filho, R.; Stinghen, A.E.M. Uremia Impacts VE-Cadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions. Toxins 2018, 10, 404.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top