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TNF causes changes in glomerular endothelial permeability and morphology through a Rho and myosin light chain kinase‐dependent mechanism
A key function of the endothelium is to serve as a regulated barrier between tissue compartments. We have previously shown that tumor necrosis factor (TNF) plays a crucial role in lipopolysaccharide (LPS)‐induced acute kidney injury, in part by causing injury to the renal endothelium through its rec...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760430/ https://www.ncbi.nlm.nih.gov/pubmed/26634902 http://dx.doi.org/10.14814/phy2.12636 |
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author | Xu, Chang Wu, Xiaoyan Hack, Bradley K. Bao, Lihua Cunningham, Patrick N. |
author_facet | Xu, Chang Wu, Xiaoyan Hack, Bradley K. Bao, Lihua Cunningham, Patrick N. |
author_sort | Xu, Chang |
collection | PubMed |
description | A key function of the endothelium is to serve as a regulated barrier between tissue compartments. We have previously shown that tumor necrosis factor (TNF) plays a crucial role in lipopolysaccharide (LPS)‐induced acute kidney injury, in part by causing injury to the renal endothelium through its receptor TNFR1. Here, we report that TNF increased permeability to albumin in primary culture mouse renal endothelial cells, as well as human glomerular endothelial cells. This process occurred in association with changes in the actin cytoskeleton and was associated with gaps between previously confluent cells in culture and decreases in the tight junction protein occludin. This process was dependent on myosin light chain activation, as seen by its prevention with Rho‐associated kinase and myosin light chain kinase (MLCK) inhibitors. Surprisingly, permeability was not blocked by inhibition of apoptosis with caspase inhibitors. Additionally, we found that the renal glycocalyx, which plays an important role in barrier function, was also degraded by TNF in a Rho and MLCK dependent fashion. TNF treatment caused a decrease in the size of endothelial fenestrae, dependent on Rho and MLCK, although the relevance of this to changes in permeability is uncertain. In summary, TNF‐induced barrier dysfunction in renal endothelial cells is crucially dependent upon the Rho/MLCK signaling pathway. |
format | Online Article Text |
id | pubmed-4760430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-47604302016-02-22 TNF causes changes in glomerular endothelial permeability and morphology through a Rho and myosin light chain kinase‐dependent mechanism Xu, Chang Wu, Xiaoyan Hack, Bradley K. Bao, Lihua Cunningham, Patrick N. Physiol Rep Original Research A key function of the endothelium is to serve as a regulated barrier between tissue compartments. We have previously shown that tumor necrosis factor (TNF) plays a crucial role in lipopolysaccharide (LPS)‐induced acute kidney injury, in part by causing injury to the renal endothelium through its receptor TNFR1. Here, we report that TNF increased permeability to albumin in primary culture mouse renal endothelial cells, as well as human glomerular endothelial cells. This process occurred in association with changes in the actin cytoskeleton and was associated with gaps between previously confluent cells in culture and decreases in the tight junction protein occludin. This process was dependent on myosin light chain activation, as seen by its prevention with Rho‐associated kinase and myosin light chain kinase (MLCK) inhibitors. Surprisingly, permeability was not blocked by inhibition of apoptosis with caspase inhibitors. Additionally, we found that the renal glycocalyx, which plays an important role in barrier function, was also degraded by TNF in a Rho and MLCK dependent fashion. TNF treatment caused a decrease in the size of endothelial fenestrae, dependent on Rho and MLCK, although the relevance of this to changes in permeability is uncertain. In summary, TNF‐induced barrier dysfunction in renal endothelial cells is crucially dependent upon the Rho/MLCK signaling pathway. John Wiley and Sons Inc. 2015-12-03 /pmc/articles/PMC4760430/ /pubmed/26634902 http://dx.doi.org/10.14814/phy2.12636 Text en © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Xu, Chang Wu, Xiaoyan Hack, Bradley K. Bao, Lihua Cunningham, Patrick N. TNF causes changes in glomerular endothelial permeability and morphology through a Rho and myosin light chain kinase‐dependent mechanism |
title | TNF causes changes in glomerular endothelial permeability and morphology through a Rho and myosin light chain kinase‐dependent mechanism |
title_full | TNF causes changes in glomerular endothelial permeability and morphology through a Rho and myosin light chain kinase‐dependent mechanism |
title_fullStr | TNF causes changes in glomerular endothelial permeability and morphology through a Rho and myosin light chain kinase‐dependent mechanism |
title_full_unstemmed | TNF causes changes in glomerular endothelial permeability and morphology through a Rho and myosin light chain kinase‐dependent mechanism |
title_short | TNF causes changes in glomerular endothelial permeability and morphology through a Rho and myosin light chain kinase‐dependent mechanism |
title_sort | tnf causes changes in glomerular endothelial permeability and morphology through a rho and myosin light chain kinase‐dependent mechanism |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760430/ https://www.ncbi.nlm.nih.gov/pubmed/26634902 http://dx.doi.org/10.14814/phy2.12636 |
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