Coordination of the cell cycle is an important determinant of the syndrome of acute renal failure.
Recovery from injury is usually accompanied by cell replication, in which new cells replace those irreparably damaged. After acute renal failure, normally quiescent kidney cells enter the cell cycle, which in tubule segments is accompanied by the induction of cell cycle inhibitors. We found that after acute renal failure induced by either cisplatin injection or renal ischemia, induction of the p21 cyclin-dependent kinase (cdk) inhibitor is protective. Mice lacking this gene developed more widespread kidney cell death, more severe renal failure, and had reduced survival, compared with mice with a functional p21 gene. Here, we show induction of 14-3-3sigma, a regulator of G(2)-to-M transition, after acute renal failure. Our findings, using both in vivo and in vitro models of acute renal failure, show that this protein likely helps to coordinate cell cycle activity to maximize recovery of renal epithelial cells from injury and reduce the extent of the injury itself. Because in terminally differentiated cells, these proteins are highly expressed only after injury, we propose that cell cycle coordination by induction of these proteins could be a general model of tissue recovery from stress and injury.
Megyesi
Judit
J
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Andrade
Lucia
L
Vieira
Jose M
JM
Safirstein
Robert L
RL
Price
Peter M
PM
D058186:Acute Kidney Injury / Q000473:pathology*; D000818:Animals; D015152:Blotting, Northern; D002453:Cell Cycle / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D002467:Cell Nucleus / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity; D017403:In Situ Hybridization; D007668:Kidney / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D015689:Oncogene Protein p21(ras) / Q000235:genetics; D016877:Oxidants / Q000633:toxicity; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis
D016877:Oxidants; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D015689:Oncogene Protein p21(ras); D002945:Cisplatin