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Loss of Endothelial Barrier Function in the Inflammatory Setting: Indication for a Cytokine-Mediated Post-Transcriptional Mechanism by Virtue of Upregulation of miRNAs miR-29a-3p, miR-29b-3p, and miR-155-5p
Dysfunction of the endothelial barrier plays a central role in the pathogenesis of both acute and chronic inflammatory processes such as sepsis or atherosclerosis. Due to attenuation of endothelial cell contacts, there is an increased transfer of blood proteins and fluid into the surrounding tissue,...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616298/ https://www.ncbi.nlm.nih.gov/pubmed/34831066 http://dx.doi.org/10.3390/cells10112843 |
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author | Maucher, Daniel Schmidt, Birte Schumann, Julia |
author_facet | Maucher, Daniel Schmidt, Birte Schumann, Julia |
author_sort | Maucher, Daniel |
collection | PubMed |
description | Dysfunction of the endothelial barrier plays a central role in the pathogenesis of both acute and chronic inflammatory processes such as sepsis or atherosclerosis. Due to attenuation of endothelial cell contacts, there is an increased transfer of blood proteins and fluid into the surrounding tissue, which relates to edema formation and distribution disorders. However, the mechanisms underlying these responses are not fully understood. In this study, we used human endothelial cells to mimic the loss of barrier function in an inflammatory milieu. We found that a weakened endothelial barrier after cytokine stimulation was accompanied by a significantly changed transcriptome. Apparent was a depletion of mRNAs encoding cell adhesion molecules. Furthermore, we found that cytokine treatment of endothelial cells induced upregulation of miR-29a-3p, miR-29b-3p, and miR-155-5p. miRNAs are known to negatively affect stability and translational efficiency of target mRNAs. Remarkably, miR-29a-3p, miR-29b-3p, and miR-155-5p have already been described to target the mRNAs of central tight and adherent junction proteins including F11 receptor, claudin 1, β-catenin, p120-catenin, and eplin. This taken together points to the existence of a posttranscriptional mechanism for expression inhibition of central adhesion proteins, which is triggered by inflammatory cytokines and mediated by miR-29a-3p, miR-29b-3p, and miR-155-5p. |
format | Online Article Text |
id | pubmed-8616298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86162982021-11-26 Loss of Endothelial Barrier Function in the Inflammatory Setting: Indication for a Cytokine-Mediated Post-Transcriptional Mechanism by Virtue of Upregulation of miRNAs miR-29a-3p, miR-29b-3p, and miR-155-5p Maucher, Daniel Schmidt, Birte Schumann, Julia Cells Article Dysfunction of the endothelial barrier plays a central role in the pathogenesis of both acute and chronic inflammatory processes such as sepsis or atherosclerosis. Due to attenuation of endothelial cell contacts, there is an increased transfer of blood proteins and fluid into the surrounding tissue, which relates to edema formation and distribution disorders. However, the mechanisms underlying these responses are not fully understood. In this study, we used human endothelial cells to mimic the loss of barrier function in an inflammatory milieu. We found that a weakened endothelial barrier after cytokine stimulation was accompanied by a significantly changed transcriptome. Apparent was a depletion of mRNAs encoding cell adhesion molecules. Furthermore, we found that cytokine treatment of endothelial cells induced upregulation of miR-29a-3p, miR-29b-3p, and miR-155-5p. miRNAs are known to negatively affect stability and translational efficiency of target mRNAs. Remarkably, miR-29a-3p, miR-29b-3p, and miR-155-5p have already been described to target the mRNAs of central tight and adherent junction proteins including F11 receptor, claudin 1, β-catenin, p120-catenin, and eplin. This taken together points to the existence of a posttranscriptional mechanism for expression inhibition of central adhesion proteins, which is triggered by inflammatory cytokines and mediated by miR-29a-3p, miR-29b-3p, and miR-155-5p. MDPI 2021-10-22 /pmc/articles/PMC8616298/ /pubmed/34831066 http://dx.doi.org/10.3390/cells10112843 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Maucher, Daniel Schmidt, Birte Schumann, Julia Loss of Endothelial Barrier Function in the Inflammatory Setting: Indication for a Cytokine-Mediated Post-Transcriptional Mechanism by Virtue of Upregulation of miRNAs miR-29a-3p, miR-29b-3p, and miR-155-5p |
title | Loss of Endothelial Barrier Function in the Inflammatory Setting: Indication for a Cytokine-Mediated Post-Transcriptional Mechanism by Virtue of Upregulation of miRNAs miR-29a-3p, miR-29b-3p, and miR-155-5p |
title_full | Loss of Endothelial Barrier Function in the Inflammatory Setting: Indication for a Cytokine-Mediated Post-Transcriptional Mechanism by Virtue of Upregulation of miRNAs miR-29a-3p, miR-29b-3p, and miR-155-5p |
title_fullStr | Loss of Endothelial Barrier Function in the Inflammatory Setting: Indication for a Cytokine-Mediated Post-Transcriptional Mechanism by Virtue of Upregulation of miRNAs miR-29a-3p, miR-29b-3p, and miR-155-5p |
title_full_unstemmed | Loss of Endothelial Barrier Function in the Inflammatory Setting: Indication for a Cytokine-Mediated Post-Transcriptional Mechanism by Virtue of Upregulation of miRNAs miR-29a-3p, miR-29b-3p, and miR-155-5p |
title_short | Loss of Endothelial Barrier Function in the Inflammatory Setting: Indication for a Cytokine-Mediated Post-Transcriptional Mechanism by Virtue of Upregulation of miRNAs miR-29a-3p, miR-29b-3p, and miR-155-5p |
title_sort | loss of endothelial barrier function in the inflammatory setting: indication for a cytokine-mediated post-transcriptional mechanism by virtue of upregulation of mirnas mir-29a-3p, mir-29b-3p, and mir-155-5p |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616298/ https://www.ncbi.nlm.nih.gov/pubmed/34831066 http://dx.doi.org/10.3390/cells10112843 |
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