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Int. J. Mol. Sci. 2018, 19(7), 2038;

Epithelial Cell Cycle Behaviour in the Injured Kidney

Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, 2000 Antwerp, Belgium
Author to whom correspondence should be addressed.
Received: 10 June 2018 / Accepted: 10 July 2018 / Published: 13 July 2018
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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. View Full-Text
Keywords: AKI; CKD; cell cycle; proximal epithelium cell; G1/S arrest; G2/M arrest AKI; CKD; cell cycle; proximal epithelium cell; G1/S arrest; G2/M arrest

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Moonen, L.; D’Haese, P.C.; Vervaet, B.A. Epithelial Cell Cycle Behaviour in the Injured Kidney. Int. J. Mol. Sci. 2018, 19, 2038.

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