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Metabolic stress promotes renal tubular inflammation by triggering the unfolded protein response

The renal epithelium contributes to the development of inflammation during ischemic injury. Ischemia induces endoplasmic reticulum (ER) stress and activates the unfolded protein response (UPR). Ischemic tissues generate distress signals and inflammation that activates fibrogenesis and may promote ad...

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Autores principales: Fougeray, S, Bouvier, N, Beaune, P, Legendre, C, Anglicheau, D, Thervet, E, Pallet, N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122058/
https://www.ncbi.nlm.nih.gov/pubmed/21490675
http://dx.doi.org/10.1038/cddis.2011.26
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author Fougeray, S
Bouvier, N
Beaune, P
Legendre, C
Anglicheau, D
Thervet, E
Pallet, N
author_facet Fougeray, S
Bouvier, N
Beaune, P
Legendre, C
Anglicheau, D
Thervet, E
Pallet, N
author_sort Fougeray, S
collection PubMed
description The renal epithelium contributes to the development of inflammation during ischemic injury. Ischemia induces endoplasmic reticulum (ER) stress and activates the unfolded protein response (UPR). Ischemic tissues generate distress signals and inflammation that activates fibrogenesis and may promote adaptive immunity. Interestingly, the UPR may activate inflammation pathways. Our aim was to test whether the UPR is activated during metabolic stress and mediates a tubular inflammatory response. Glucose deprivation, not hypoxia and amino acids deprivation, activated the UPR in human renal cortical tubular cells in culture. This stress activated NF-κB and promoted the transcription of proinflammatory cytokines and chemokines, including IL-6, IL-8, TNF-α, RANTES and MCP-1. The protein kinase RNA (PKR)-like ER kinase signaling pathway was not required for the induction of inflammation but amplified cytokine. Inositol-requiring enzyme 1 activated NF-κB signaling and was required for the transcription of proinflammatory cytokines and chemokines following metabolic stress. Moreover, acute ischemia activated ER stress and inflammation in rat kidneys. Finally, the ER stress marker GRP78 and NF-κB p65/RelA were coexpressed in human kidney transplants biopsies performed before implantation, suggesting that ER stress activates tubular inflammation in human renal allografts. In conclusion, this study establishes a link between ischemic stress, the activation of the UPR and the generation of a tubular inflammatory response.
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spelling pubmed-31220582011-07-05 Metabolic stress promotes renal tubular inflammation by triggering the unfolded protein response Fougeray, S Bouvier, N Beaune, P Legendre, C Anglicheau, D Thervet, E Pallet, N Cell Death Dis Original Article The renal epithelium contributes to the development of inflammation during ischemic injury. Ischemia induces endoplasmic reticulum (ER) stress and activates the unfolded protein response (UPR). Ischemic tissues generate distress signals and inflammation that activates fibrogenesis and may promote adaptive immunity. Interestingly, the UPR may activate inflammation pathways. Our aim was to test whether the UPR is activated during metabolic stress and mediates a tubular inflammatory response. Glucose deprivation, not hypoxia and amino acids deprivation, activated the UPR in human renal cortical tubular cells in culture. This stress activated NF-κB and promoted the transcription of proinflammatory cytokines and chemokines, including IL-6, IL-8, TNF-α, RANTES and MCP-1. The protein kinase RNA (PKR)-like ER kinase signaling pathway was not required for the induction of inflammation but amplified cytokine. Inositol-requiring enzyme 1 activated NF-κB signaling and was required for the transcription of proinflammatory cytokines and chemokines following metabolic stress. Moreover, acute ischemia activated ER stress and inflammation in rat kidneys. Finally, the ER stress marker GRP78 and NF-κB p65/RelA were coexpressed in human kidney transplants biopsies performed before implantation, suggesting that ER stress activates tubular inflammation in human renal allografts. In conclusion, this study establishes a link between ischemic stress, the activation of the UPR and the generation of a tubular inflammatory response. Nature Publishing Group 2011-04 2011-04-14 /pmc/articles/PMC3122058/ /pubmed/21490675 http://dx.doi.org/10.1038/cddis.2011.26 Text en Copyright © 2011 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Fougeray, S
Bouvier, N
Beaune, P
Legendre, C
Anglicheau, D
Thervet, E
Pallet, N
Metabolic stress promotes renal tubular inflammation by triggering the unfolded protein response
title Metabolic stress promotes renal tubular inflammation by triggering the unfolded protein response
title_full Metabolic stress promotes renal tubular inflammation by triggering the unfolded protein response
title_fullStr Metabolic stress promotes renal tubular inflammation by triggering the unfolded protein response
title_full_unstemmed Metabolic stress promotes renal tubular inflammation by triggering the unfolded protein response
title_short Metabolic stress promotes renal tubular inflammation by triggering the unfolded protein response
title_sort metabolic stress promotes renal tubular inflammation by triggering the unfolded protein response
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122058/
https://www.ncbi.nlm.nih.gov/pubmed/21490675
http://dx.doi.org/10.1038/cddis.2011.26
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