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Epithelial Cell Cycle Behaviour in the Injured Kidney
Acute kidney injury (AKI), commonly caused by ischemia-reperfusion injury, has far-reaching health consequences. Despite the significant regenerative capacity of proximal tubular epithelium cells (PTCs), repair frequently fails, leading to the development of chronic kidney disease (CKD). In the last...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073451/ https://www.ncbi.nlm.nih.gov/pubmed/30011818 http://dx.doi.org/10.3390/ijms19072038 |
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author | Moonen, Lies D’Haese, Patrick C. Vervaet, Benjamin A. |
author_facet | Moonen, Lies D’Haese, Patrick C. Vervaet, Benjamin A. |
author_sort | Moonen, Lies |
collection | PubMed |
description | Acute kidney injury (AKI), commonly caused by ischemia-reperfusion injury, has far-reaching health consequences. Despite the significant regenerative capacity of proximal tubular epithelium cells (PTCs), repair frequently fails, leading to the development of chronic kidney disease (CKD). In the last decade, it has been repeatedly demonstrated that dysregulation of the cell cycle can cause injured kidneys to progress to CKD. More precisely, severe AKI causes PTCs to arrest in the G1/S or G2/M phase of the cell cycle, leading to maladaptive repair and a fibrotic outcome. The mechanisms causing these arrests are far from known. The arrest might, at least partially, be attributed to DNA damage since activation of the DNA-damage response pathway leads to cell cycle arrest. Alternatively, cytokine signalling via nuclear factor kappa beta (NF-κβ) and p38-mitogen-activated protein kinase (p38-MAPK) pathways, and reactive oxygen species (ROS) can play a role independent of DNA damage. In addition, only a handful of cell cycle regulators (e.g., p53, p21) have been thoroughly studied during renal repair. Still, why and how PTCs decide to arrest their cell cycle and how this arrest can efficiently be overcome remain open and challenging questions. In this review we will discuss the evidence for cell cycle involvement during AKI and development of CKD together with putative therapeutic approaches. |
format | Online Article Text |
id | pubmed-6073451 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-60734512018-08-13 Epithelial Cell Cycle Behaviour in the Injured Kidney Moonen, Lies D’Haese, Patrick C. Vervaet, Benjamin A. Int J Mol Sci Review Acute kidney injury (AKI), commonly caused by ischemia-reperfusion injury, has far-reaching health consequences. Despite the significant regenerative capacity of proximal tubular epithelium cells (PTCs), repair frequently fails, leading to the development of chronic kidney disease (CKD). In the last decade, it has been repeatedly demonstrated that dysregulation of the cell cycle can cause injured kidneys to progress to CKD. More precisely, severe AKI causes PTCs to arrest in the G1/S or G2/M phase of the cell cycle, leading to maladaptive repair and a fibrotic outcome. The mechanisms causing these arrests are far from known. The arrest might, at least partially, be attributed to DNA damage since activation of the DNA-damage response pathway leads to cell cycle arrest. Alternatively, cytokine signalling via nuclear factor kappa beta (NF-κβ) and p38-mitogen-activated protein kinase (p38-MAPK) pathways, and reactive oxygen species (ROS) can play a role independent of DNA damage. In addition, only a handful of cell cycle regulators (e.g., p53, p21) have been thoroughly studied during renal repair. Still, why and how PTCs decide to arrest their cell cycle and how this arrest can efficiently be overcome remain open and challenging questions. In this review we will discuss the evidence for cell cycle involvement during AKI and development of CKD together with putative therapeutic approaches. MDPI 2018-07-13 /pmc/articles/PMC6073451/ /pubmed/30011818 http://dx.doi.org/10.3390/ijms19072038 Text en © 2018 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 | Review Moonen, Lies D’Haese, Patrick C. Vervaet, Benjamin A. Epithelial Cell Cycle Behaviour in the Injured Kidney |
title | Epithelial Cell Cycle Behaviour in the Injured Kidney |
title_full | Epithelial Cell Cycle Behaviour in the Injured Kidney |
title_fullStr | Epithelial Cell Cycle Behaviour in the Injured Kidney |
title_full_unstemmed | Epithelial Cell Cycle Behaviour in the Injured Kidney |
title_short | Epithelial Cell Cycle Behaviour in the Injured Kidney |
title_sort | epithelial cell cycle behaviour in the injured kidney |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073451/ https://www.ncbi.nlm.nih.gov/pubmed/30011818 http://dx.doi.org/10.3390/ijms19072038 |
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