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Comprehensive transcriptome analysis of fluid shear stress altered gene expression in renal epithelial cells

Renal epithelial cells are exposed to mechanical forces due to flow‐induced shear stress within the nephrons. Shear stress is altered in renal diseases caused by tubular dilation, obstruction, and hyperfiltration, which occur to compensate for lost nephrons. Fundamental in regulation of shear stress...

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Autores principales: Kunnen, Steven J., Malas, Tareq B., Semeins, Cornelis M., Bakker, Astrid D., Peters, Dorien J. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765508/
https://www.ncbi.nlm.nih.gov/pubmed/29044509
http://dx.doi.org/10.1002/jcp.26222
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author Kunnen, Steven J.
Malas, Tareq B.
Semeins, Cornelis M.
Bakker, Astrid D.
Peters, Dorien J. M.
author_facet Kunnen, Steven J.
Malas, Tareq B.
Semeins, Cornelis M.
Bakker, Astrid D.
Peters, Dorien J. M.
author_sort Kunnen, Steven J.
collection PubMed
description Renal epithelial cells are exposed to mechanical forces due to flow‐induced shear stress within the nephrons. Shear stress is altered in renal diseases caused by tubular dilation, obstruction, and hyperfiltration, which occur to compensate for lost nephrons. Fundamental in regulation of shear stress are primary cilia and other mechano‐sensors, and defects in cilia formation and function have profound effects on development and physiology of kidneys and other organs. We applied RNA sequencing to get a comprehensive overview of fluid‐shear regulated genes and pathways in renal epithelial cells. Functional enrichment‐analysis revealed TGF‐β, MAPK, and Wnt signaling as core signaling pathways up‐regulated by shear. Inhibitors of TGF‐β and MAPK/ERK signaling modulate a wide range of mechanosensitive genes, identifying these pathways as master regulators of shear‐induced gene expression. However, the main down‐regulated pathway, that is, JAK/STAT, is independent of TGF‐β and MAPK/ERK. Other up‐regulated cytokine pathways include FGF, HB‐EGF, PDGF, and CXC. Cellular responses to shear are modified at several levels, indicated by altered expression of genes involved in cell‐matrix, cytoskeleton, and glycocalyx remodeling, as well as glycolysis and cholesterol metabolism. Cilia ablation abolished shear induced expression of a subset of genes, but genes involved in TGF‐β, MAPK, and Wnt signaling were hardly affected, suggesting that other mechano‐sensors play a prominent role in the shear stress response of renal epithelial cells. Modulations in signaling due to variations in fluid shear stress are relevant for renal physiology and pathology, as suggested by elevated gene expression at pathological levels of shear stress compared to physiological shear.
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spelling pubmed-57655082018-02-01 Comprehensive transcriptome analysis of fluid shear stress altered gene expression in renal epithelial cells Kunnen, Steven J. Malas, Tareq B. Semeins, Cornelis M. Bakker, Astrid D. Peters, Dorien J. M. J Cell Physiol Original Research Articles Renal epithelial cells are exposed to mechanical forces due to flow‐induced shear stress within the nephrons. Shear stress is altered in renal diseases caused by tubular dilation, obstruction, and hyperfiltration, which occur to compensate for lost nephrons. Fundamental in regulation of shear stress are primary cilia and other mechano‐sensors, and defects in cilia formation and function have profound effects on development and physiology of kidneys and other organs. We applied RNA sequencing to get a comprehensive overview of fluid‐shear regulated genes and pathways in renal epithelial cells. Functional enrichment‐analysis revealed TGF‐β, MAPK, and Wnt signaling as core signaling pathways up‐regulated by shear. Inhibitors of TGF‐β and MAPK/ERK signaling modulate a wide range of mechanosensitive genes, identifying these pathways as master regulators of shear‐induced gene expression. However, the main down‐regulated pathway, that is, JAK/STAT, is independent of TGF‐β and MAPK/ERK. Other up‐regulated cytokine pathways include FGF, HB‐EGF, PDGF, and CXC. Cellular responses to shear are modified at several levels, indicated by altered expression of genes involved in cell‐matrix, cytoskeleton, and glycocalyx remodeling, as well as glycolysis and cholesterol metabolism. Cilia ablation abolished shear induced expression of a subset of genes, but genes involved in TGF‐β, MAPK, and Wnt signaling were hardly affected, suggesting that other mechano‐sensors play a prominent role in the shear stress response of renal epithelial cells. Modulations in signaling due to variations in fluid shear stress are relevant for renal physiology and pathology, as suggested by elevated gene expression at pathological levels of shear stress compared to physiological shear. John Wiley and Sons Inc. 2017-11-20 2018-04 /pmc/articles/PMC5765508/ /pubmed/29044509 http://dx.doi.org/10.1002/jcp.26222 Text en © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. 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 Articles
Kunnen, Steven J.
Malas, Tareq B.
Semeins, Cornelis M.
Bakker, Astrid D.
Peters, Dorien J. M.
Comprehensive transcriptome analysis of fluid shear stress altered gene expression in renal epithelial cells
title Comprehensive transcriptome analysis of fluid shear stress altered gene expression in renal epithelial cells
title_full Comprehensive transcriptome analysis of fluid shear stress altered gene expression in renal epithelial cells
title_fullStr Comprehensive transcriptome analysis of fluid shear stress altered gene expression in renal epithelial cells
title_full_unstemmed Comprehensive transcriptome analysis of fluid shear stress altered gene expression in renal epithelial cells
title_short Comprehensive transcriptome analysis of fluid shear stress altered gene expression in renal epithelial cells
title_sort comprehensive transcriptome analysis of fluid shear stress altered gene expression in renal epithelial cells
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765508/
https://www.ncbi.nlm.nih.gov/pubmed/29044509
http://dx.doi.org/10.1002/jcp.26222
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