'Biologic memory' in response to acute kidney injury: cytoresistance, toll-like receptor hyper-responsiveness and the onset of progressive renal disease.
'Biologic memory' in response to acute kidney injury: cytoresistance, toll-like receptor hyper-responsiveness and the onset of progressive renal disease.
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DOI：
10.1093/ndt/gft101
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发表时间：
2013-08
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影响因子：
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通讯作者：
R. Zager
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文献类型：
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作者：
R. Zager
在诱导缺血性或毒素介导的急性肾损伤（阿基）后，细胞适应发生，“重新编程”肾脏如何对未来叠加的损伤做出反应。这种重新编程不仅仅是一种短暂的现象;相反，它可以持续数周，这意味着一种“生物记忆”的状态已经出现。这些变化在本质上既可以是适应性的，也可以是适应不良的，它们可以在时间上共存。一种有益的适应是获得性细胞耐药性的出现，由此产生许多生理反应，有助于保护肾脏免受进一步的缺血或肾毒性攻击。相反，一些变化是适应不良的，例如由于肾小管上调toll样受体反应而导致的革兰氏阴性或革兰氏阳性菌血症的易感性。后一种变化最终导致细胞因子产生过度，并流出到体循环中，可能导致肾外组织损伤（所谓的“器官串扰”）。另一种适应不良反应是促炎、促纤维化和血管收缩基因的持续上调，最终导致进行性肾损伤和终末期肾衰竭。这种生物重新编程或生物记忆的机制仍然是相当多争论的主题。然而，促炎症/促纤维化基因的损伤诱导的、稳定的表观遗传重塑似乎可能参与其中。这篇社论的目的是强调所谓的急性肾衰竭的“维持期”并不是一个静态的，介于损伤诱导和修复开始之间。相反，在此期间，“生物记忆”的诱导可能最终影响肾功能恢复、肾外损伤以及阿基可能转变为慢性进行性肾病。
Following the induction of ischemic or toxin-mediated acute kidney injury (AKI), cellular adaptations occur that 're-program' how the kidney responds to future superimposed insults. This re-programming is not simply a short-lived phenomenon; rather it can persist for many weeks, implying that a state of 'biologic memory' has emerged. These changes can be both adaptive and maladaptive in nature and they can co-exist in time. A beneficial adaptation is the emergence of acquired cytoresistance, whereby a number of physiologic responses develop that serve to protect the kidney against further ischemic or nephrotoxic attack. Conversely, some changes are maladaptive, such as a predisposition to Gram-negative or Gram-positive bacteremia due to a renal tubular up-regulation of toll-like receptor responses. This latter change culminates in exaggerated cytokine production, and with efflux into the systemic circulation, extra-renal tissue injury can result (so-called 'organ cross talk'). Another maladaptive response is a persistent up-regulation of pro-inflammatory, pro-fibrotic and vasoconstrictive genes, culminating in progressive renal injury and ultimately end-stage renal failure. The mechanisms by which this biologic re-programming, or biologic memory, is imparted remain subjects for considerable debate. However, injury-induced, and stable, epigenetic remodeling at pro-inflammatory/pro-fibrotic genes seems likely to be involved. The goal of this editorial is to highlight that the so-called 'maintenance phase' of acute renal failure is not a static one, somewhere between injury induction and the onset of repair. Rather, this period is one in which the induction of 'biologic memory' can ultimately impact renal functional recovery, extra-renal injury and the possible transition of AKI into chronic, progressive renal disease.