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Autophagy Dynamics and Modulation in a Rat Model of Renal Ischemia-Reperfusion Injury

Renal ischemia-reperfusion (IR) injury leading to cell death is a major cause of acute kidney injury, contributing to morbidity and mortality. Autophagy counteracts cell death by removing damaged macromolecules and organelles, making it an interesting anchor point for treatment strategies. However,...

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Autores principales: Decuypere, Jean-Paul, Hutchinson, Shawn, Monbaliu, Diethard, Martinet, Wim, Pirenne, Jacques, Jochmans, Ina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583807/
https://www.ncbi.nlm.nih.gov/pubmed/33003356
http://dx.doi.org/10.3390/ijms21197185
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author Decuypere, Jean-Paul
Hutchinson, Shawn
Monbaliu, Diethard
Martinet, Wim
Pirenne, Jacques
Jochmans, Ina
author_facet Decuypere, Jean-Paul
Hutchinson, Shawn
Monbaliu, Diethard
Martinet, Wim
Pirenne, Jacques
Jochmans, Ina
author_sort Decuypere, Jean-Paul
collection PubMed
description Renal ischemia-reperfusion (IR) injury leading to cell death is a major cause of acute kidney injury, contributing to morbidity and mortality. Autophagy counteracts cell death by removing damaged macromolecules and organelles, making it an interesting anchor point for treatment strategies. However, autophagy is also suggested to enhance cell death when the ischemic burden is too strong. To investigate whether the role of autophagy depends on the severity of ischemic stress, we analyzed the dynamics of autophagy and apoptosis in an IR rat model with mild (45 min) or severe (60 min) renal ischemia. Following mild IR, renal injury was associated with reduced autophagy, enhanced mammalian target of rapamycin (mTOR) activity, and apoptosis. Severe IR, on the other hand, was associated with a higher autophagic activity, independent of mTOR, and without affecting apoptosis. Autophagy stimulation by trehalose injected 24 and 48 h prior to onset of severe ischemia did not reduce renal injury markers nor function, but reduced apoptosis and restored tubular dilation 7 days post reperfusion. This suggests that trehalose-dependent autophagy stimulation enhances tissue repair following an IR injury. Our data show that autophagy dynamics are strongly dependent on the severity of IR and that trehalose shows the potential to trigger autophagy-dependent repair processes following renal IR injury.
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spelling pubmed-75838072020-10-28 Autophagy Dynamics and Modulation in a Rat Model of Renal Ischemia-Reperfusion Injury Decuypere, Jean-Paul Hutchinson, Shawn Monbaliu, Diethard Martinet, Wim Pirenne, Jacques Jochmans, Ina Int J Mol Sci Article Renal ischemia-reperfusion (IR) injury leading to cell death is a major cause of acute kidney injury, contributing to morbidity and mortality. Autophagy counteracts cell death by removing damaged macromolecules and organelles, making it an interesting anchor point for treatment strategies. However, autophagy is also suggested to enhance cell death when the ischemic burden is too strong. To investigate whether the role of autophagy depends on the severity of ischemic stress, we analyzed the dynamics of autophagy and apoptosis in an IR rat model with mild (45 min) or severe (60 min) renal ischemia. Following mild IR, renal injury was associated with reduced autophagy, enhanced mammalian target of rapamycin (mTOR) activity, and apoptosis. Severe IR, on the other hand, was associated with a higher autophagic activity, independent of mTOR, and without affecting apoptosis. Autophagy stimulation by trehalose injected 24 and 48 h prior to onset of severe ischemia did not reduce renal injury markers nor function, but reduced apoptosis and restored tubular dilation 7 days post reperfusion. This suggests that trehalose-dependent autophagy stimulation enhances tissue repair following an IR injury. Our data show that autophagy dynamics are strongly dependent on the severity of IR and that trehalose shows the potential to trigger autophagy-dependent repair processes following renal IR injury. MDPI 2020-09-29 /pmc/articles/PMC7583807/ /pubmed/33003356 http://dx.doi.org/10.3390/ijms21197185 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Decuypere, Jean-Paul
Hutchinson, Shawn
Monbaliu, Diethard
Martinet, Wim
Pirenne, Jacques
Jochmans, Ina
Autophagy Dynamics and Modulation in a Rat Model of Renal Ischemia-Reperfusion Injury
title Autophagy Dynamics and Modulation in a Rat Model of Renal Ischemia-Reperfusion Injury
title_full Autophagy Dynamics and Modulation in a Rat Model of Renal Ischemia-Reperfusion Injury
title_fullStr Autophagy Dynamics and Modulation in a Rat Model of Renal Ischemia-Reperfusion Injury
title_full_unstemmed Autophagy Dynamics and Modulation in a Rat Model of Renal Ischemia-Reperfusion Injury
title_short Autophagy Dynamics and Modulation in a Rat Model of Renal Ischemia-Reperfusion Injury
title_sort autophagy dynamics and modulation in a rat model of renal ischemia-reperfusion injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583807/
https://www.ncbi.nlm.nih.gov/pubmed/33003356
http://dx.doi.org/10.3390/ijms21197185
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