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,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Daniel Maucher, Birte Schmidt, Julia Schumann
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	endothelial barrier miRNAs tight junctions adherens junctions Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c14ffd9bdc3c43d5937eff8025c841ce
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c14ffd9bdc3c43d5937eff8025c841ce
record_format	dspace
spelling	oai:doaj.org-article:c14ffd9bdc3c43d5937eff8025c841ce2021-11-25T17:07:50ZLoss 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-155-5p10.3390/cells101128432073-4409https://doaj.org/article/c14ffd9bdc3c43d5937eff8025c841ce2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2843https://doaj.org/toc/2073-4409Dysfunction 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.Daniel MaucherBirte SchmidtJulia SchumannMDPI AGarticleendothelial barriermiRNAstight junctionsadherens junctionsBiology (General)QH301-705.5ENCells, Vol 10, Iss 2843, p 2843 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	endothelial barrier miRNAs tight junctions adherens junctions Biology (General) QH301-705.5
spellingShingle	endothelial barrier miRNAs tight junctions adherens junctions Biology (General) QH301-705.5 Daniel Maucher Birte Schmidt Julia Schumann 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
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	article
author	Daniel Maucher Birte Schmidt Julia Schumann
author_facet	Daniel Maucher Birte Schmidt Julia Schumann
author_sort	Daniel Maucher
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_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_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_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
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c14ffd9bdc3c43d5937eff8025c841ce
work_keys_str_mv	AT danielmaucher lossofendothelialbarrierfunctionintheinflammatorysettingindicationforacytokinemediatedposttranscriptionalmechanismbyvirtueofupregulationofmirnasmir29a3pmir29b3pandmir1555p AT birteschmidt lossofendothelialbarrierfunctionintheinflammatorysettingindicationforacytokinemediatedposttranscriptionalmechanismbyvirtueofupregulationofmirnasmir29a3pmir29b3pandmir1555p AT juliaschumann lossofendothelialbarrierfunctionintheinflammatorysettingindicationforacytokinemediatedposttranscriptionalmechanismbyvirtueofupregulationofmirnasmir29a3pmir29b3pandmir1555p
_version_	1718412739283517440

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

Ejemplares similares