Epithelial Cell Cycle Behaviour in the Injured Kidney
AbstractAcute 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
Share & Cite This Article
Moonen, L.; D’Haese, P.C.; Vervaet, B.A. Epithelial Cell Cycle Behaviour in the Injured Kidney. Int. J. Mol. Sci. 2018, 19, 2038.
Moonen L, D’Haese PC, Vervaet BA. Epithelial Cell Cycle Behaviour in the Injured Kidney. International Journal of Molecular Sciences. 2018; 19(7):2038.Chicago/Turabian Style
Moonen, Lies; D’Haese, Patrick C.; Vervaet, Benjamin A. 2018. "Epithelial Cell Cycle Behaviour in the Injured Kidney." Int. J. Mol. Sci. 19, no. 7: 2038.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.