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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,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7583807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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