Safirstein R
Department of Medicine, University of Texas Medical Branch at Galveston 77555-0562, USA.
Adv Ren Replace Ther. 1997 Apr;4(2 Suppl 1):38-42.
When kidneys are injured in vivo, the reaction of the renal epithelial is heterogeneous. Some cells, especially those of the proximal tubule, undergo necrosis, other cells undergo apoptosis, and still others survive the injury apparently intact. In addition, injured tubules are relined with new cells actively engaged in DNA synthesis. Nephrotoxic and ischemic renal damage also is accompanied by a typical immediate early gene (IEG) response, which does not always occur in cells that undergo DNA synthesis, suggesting that the role of the IEG response is not necessarily proliferative in this setting. The activation of parts of this pathway is mediated by the stress-activated protein kinases (SAPKs), which may induce cell-cycle arrest and apoptosis. Downregulation of the SAPKs improve renal function and improve long-term outcome during ischemic renal failure. It is thus possible that manipulation of this pathway could ameliorate acute renal failure. Clues to the pertinent pathways and genes to target therapy to alter the course of renal failure will come from continued understanding of the transduction pathways activated by renal cell stress and the identification of factors that promote survival of renal cells.
当肾脏在体内受到损伤时，肾上皮细胞的反应是异质性的。一些细胞，尤其是近端小管的细胞，会发生坏死，其他细胞会发生凋亡，还有一些细胞在损伤后似乎完好无损地存活下来。此外，受损的肾小管会被积极参与DNA合成的新细胞重新覆盖。肾毒性和缺血性肾损伤还伴随着典型的即刻早期基因（IEG）反应，而这种反应并不总是发生在进行DNA合成的细胞中，这表明在这种情况下，IEG反应的作用不一定是增殖性的。该途径部分的激活由应激激活蛋白激酶（SAPK）介导，SAPK可能诱导细胞周期停滞和凋亡。下调SAPK可改善肾功能，并改善缺血性肾衰竭的长期预后。因此，操纵该途径有可能改善急性肾衰竭。针对相关途径和基因进行靶向治疗以改变肾衰竭病程的线索将来自对肾细胞应激激活的转导途径的持续了解以及对促进肾细胞存活的因素的识别。
