Megyesi Judit, Andrade Lucia, Vieira Jose M, Safirstein Robert L, Price Peter M
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Am J Physiol Renal Physiol. 2002 Oct;283(4):F810-6. doi: 10.1152/ajprenal.00078.2002.
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.
损伤恢复通常伴随着细胞复制，即新细胞取代那些遭受不可修复损伤的细胞。急性肾衰竭后，通常处于静止状态的肾细胞进入细胞周期，在肾小管节段，这伴随着细胞周期抑制剂的诱导。我们发现，在通过顺铂注射或肾缺血诱导急性肾衰竭后，p21细胞周期蛋白依赖性激酶（cdk）抑制剂的诱导具有保护作用。与具有功能性p21基因的小鼠相比，缺乏该基因的小鼠发生了更广泛的肾细胞死亡、更严重的肾衰竭，且存活率降低。在此，我们展示了急性肾衰竭后G（2）期到M期转换的调节因子14-3-3sigma的诱导。我们使用急性肾衰竭的体内和体外模型所获得的研究结果表明，这种蛋白质可能有助于协调细胞周期活动，以使肾上皮细胞从损伤中最大限度地恢复，并减少损伤本身的程度。由于在终末分化细胞中，这些蛋白质仅在损伤后才高度表达，我们提出通过诱导这些蛋白质进行细胞周期协调可能是组织从应激和损伤中恢复的一般模式。
