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Oxidative Phosphorylation-Mediated E-Selectin Upregulation Is Associated With Endothelia–Monocyte Adhesion in Human Coronary Artery Endothelial Cells Treated With Sera From Patients With Kawasaki Disease

Background and aims: E-selectin is a cell adhesion molecule of the vascular endothelium that mediates leukocyte rolling in the early inflammatory responses in many diseases including Kawasaki disease (KD). Previous studies have demonstrated that the expression levels of E-selectin was significantly...

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Autores principales: Zhang, Danfeng, Liu, Lingjuan, Yuan, Yuxing, Lv, Tiewei, Huang, Xupei, Tian, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937974/
https://www.ncbi.nlm.nih.gov/pubmed/33692974
http://dx.doi.org/10.3389/fped.2021.618267
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author Zhang, Danfeng
Liu, Lingjuan
Yuan, Yuxing
Lv, Tiewei
Huang, Xupei
Tian, Jie
author_facet Zhang, Danfeng
Liu, Lingjuan
Yuan, Yuxing
Lv, Tiewei
Huang, Xupei
Tian, Jie
author_sort Zhang, Danfeng
collection PubMed
description Background and aims: E-selectin is a cell adhesion molecule of the vascular endothelium that mediates leukocyte rolling in the early inflammatory responses in many diseases including Kawasaki disease (KD). Previous studies have demonstrated that the expression levels of E-selectin was significantly increased in the sera of KD patients and in endothelial cells of KD patient's autopsy. In this study, we aimed to examine E-selectin levels in endothelial cells treated with sera from KD patients and explore the underlying mechanisms. Methods: Human coronary artery endothelial cells (HCAECs) were randomly incubated with sera from either healthy children [healthy control (HC group)] or pediatric KD patients [assigned as KD with coronary artery lesion (KD-CAL+ group) and KD without coronary artery lesion (KD-CAL– group)]. E-selectin levels were determined by RT-qPCR, Western blotting, and immunofluorescence. Cell adhesion assay was performed to quantify the role of E-selectin in intercellular adhesion. High-throughput cell RNA sequencing followed by functional validation was performed to explore the underlying mechanism. Results: E-selectin levels were significantly increased in KD-CAL+ group vs. HC group and KD-CAL– group. Compared with the KD-CAL– group, endothelia–monocyte adhesion was increased in the KD-CAL+ group, while E-selectin-specific siRNA could significantly rescue it. High-throughput cell RNA sequencing analysis also found a significant difference in oxidative phosphorylation (OXPHOS) levels between KD-CAL+ group and KD-CAL– group. Functional validation results further confirmed that the OXPHOS was upregulated in the KD-CAL+ group and KD-CAL– group compared to that in the HC group, while the KD-CAL+ group exhibited a higher OXPHOS than the KD-CAL– group. We also found that the E-selectin levels and endothelia–monocyte adhesion were significantly decreased by OXPHOS inhibitor oligomycin in the KD-CAL+ group and KD-CAL– group, respectively. Conclusion: Sera from KD patients stimulate OXPHOS levels and enhance E-selectin expression in HCAECs, which may contribute to the development of CAL in KD patients.
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spelling pubmed-79379742021-03-09 Oxidative Phosphorylation-Mediated E-Selectin Upregulation Is Associated With Endothelia–Monocyte Adhesion in Human Coronary Artery Endothelial Cells Treated With Sera From Patients With Kawasaki Disease Zhang, Danfeng Liu, Lingjuan Yuan, Yuxing Lv, Tiewei Huang, Xupei Tian, Jie Front Pediatr Pediatrics Background and aims: E-selectin is a cell adhesion molecule of the vascular endothelium that mediates leukocyte rolling in the early inflammatory responses in many diseases including Kawasaki disease (KD). Previous studies have demonstrated that the expression levels of E-selectin was significantly increased in the sera of KD patients and in endothelial cells of KD patient's autopsy. In this study, we aimed to examine E-selectin levels in endothelial cells treated with sera from KD patients and explore the underlying mechanisms. Methods: Human coronary artery endothelial cells (HCAECs) were randomly incubated with sera from either healthy children [healthy control (HC group)] or pediatric KD patients [assigned as KD with coronary artery lesion (KD-CAL+ group) and KD without coronary artery lesion (KD-CAL– group)]. E-selectin levels were determined by RT-qPCR, Western blotting, and immunofluorescence. Cell adhesion assay was performed to quantify the role of E-selectin in intercellular adhesion. High-throughput cell RNA sequencing followed by functional validation was performed to explore the underlying mechanism. Results: E-selectin levels were significantly increased in KD-CAL+ group vs. HC group and KD-CAL– group. Compared with the KD-CAL– group, endothelia–monocyte adhesion was increased in the KD-CAL+ group, while E-selectin-specific siRNA could significantly rescue it. High-throughput cell RNA sequencing analysis also found a significant difference in oxidative phosphorylation (OXPHOS) levels between KD-CAL+ group and KD-CAL– group. Functional validation results further confirmed that the OXPHOS was upregulated in the KD-CAL+ group and KD-CAL– group compared to that in the HC group, while the KD-CAL+ group exhibited a higher OXPHOS than the KD-CAL– group. We also found that the E-selectin levels and endothelia–monocyte adhesion were significantly decreased by OXPHOS inhibitor oligomycin in the KD-CAL+ group and KD-CAL– group, respectively. Conclusion: Sera from KD patients stimulate OXPHOS levels and enhance E-selectin expression in HCAECs, which may contribute to the development of CAL in KD patients. Frontiers Media S.A. 2021-02-22 /pmc/articles/PMC7937974/ /pubmed/33692974 http://dx.doi.org/10.3389/fped.2021.618267 Text en Copyright © 2021 Zhang, Liu, Yuan, Lv, Huang and Tian. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Pediatrics
Zhang, Danfeng
Liu, Lingjuan
Yuan, Yuxing
Lv, Tiewei
Huang, Xupei
Tian, Jie
Oxidative Phosphorylation-Mediated E-Selectin Upregulation Is Associated With Endothelia–Monocyte Adhesion in Human Coronary Artery Endothelial Cells Treated With Sera From Patients With Kawasaki Disease
title Oxidative Phosphorylation-Mediated E-Selectin Upregulation Is Associated With Endothelia–Monocyte Adhesion in Human Coronary Artery Endothelial Cells Treated With Sera From Patients With Kawasaki Disease
title_full Oxidative Phosphorylation-Mediated E-Selectin Upregulation Is Associated With Endothelia–Monocyte Adhesion in Human Coronary Artery Endothelial Cells Treated With Sera From Patients With Kawasaki Disease
title_fullStr Oxidative Phosphorylation-Mediated E-Selectin Upregulation Is Associated With Endothelia–Monocyte Adhesion in Human Coronary Artery Endothelial Cells Treated With Sera From Patients With Kawasaki Disease
title_full_unstemmed Oxidative Phosphorylation-Mediated E-Selectin Upregulation Is Associated With Endothelia–Monocyte Adhesion in Human Coronary Artery Endothelial Cells Treated With Sera From Patients With Kawasaki Disease
title_short Oxidative Phosphorylation-Mediated E-Selectin Upregulation Is Associated With Endothelia–Monocyte Adhesion in Human Coronary Artery Endothelial Cells Treated With Sera From Patients With Kawasaki Disease
title_sort oxidative phosphorylation-mediated e-selectin upregulation is associated with endothelia–monocyte adhesion in human coronary artery endothelial cells treated with sera from patients with kawasaki disease
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937974/
https://www.ncbi.nlm.nih.gov/pubmed/33692974
http://dx.doi.org/10.3389/fped.2021.618267
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