Role of Endothelial Prolyl-4-Hydroxylase Domain Protein/Hypoxia-Inducible Factor Axis in Acute Kidney Injury.
Role of Endothelial Prolyl-4-Hydroxylase Domain Protein/Hypoxia-Inducible Factor Axis in Acute Kidney Injury.
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作者：
Tiwari R;Kapitsinou PP
缺血再灌注损伤（Ischemia - reperfusion injury， IRI）是由于器官供血停止或受到限制，然后再灌注和再氧的重建。在肾脏中，移植、心脏手术合并体外循环和其他主要血管手术引起的IRI可导致急性肾损伤（AKI），这是一种与住院患者显著发病率和死亡率相关的临床疾病。在肾缺血后，内皮损伤促进炎症反应并导致肾小管上皮持续缺氧。与其他细胞类型一样，内皮细胞通过多种缺氧信号机制对低氧张力做出反应。缺氧适应的关键介质是缺氧诱导因子(HIF)-1和-2，它们的活性受到脯氨酸羟化酶结构域蛋白1至3 （PHD1至PHD3）的负调控。PHD/HIF轴控制着几个决定损伤结果的过程，包括ATP生成、细胞存活、增殖和血管生成。在这里，我们讨论了内皮来源的PHD/HIF信号及其对缺血性AKI的影响的最新进展。
Ischemia reperfusion injury (IRI) results from a cessation or restriction of blood supply to an organ followed by reestablishment of perfusion and reoxygenation. In the kidney, IRI due to transplantation, cardiac surgery with cardiopulmonary bypass, and other major vascular surgeries contributes to acute kidney injury (AKI), a clinical condition associated with significant morbidity and mortality in hospitalized patients. In the postischemic kidney, endothelial damage promotes inflammatory responses and leads to persistent hypoxia of the renal tubular epithelium. Like other cell types, endothelial cells respond to low oxygen tension by multiple hypoxic signaling mechanisms. Key mediators of adaptation to hypoxia are Hypoxia-Inducible-Factors (HIF)-1 and -2, transcription factors whose activity is negatively regulated by prolyl-hydroxylase domain proteins 1 to 3 (PHD1 to PHD3). The PHD/HIF axis controls several processes determining injury outcome, including ATP generation, cell survival, proliferation, and angiogenesis. Here, we discuss recent advances in our understanding of the endothelial derived PHD/HIF signaling and its effects on postischemic AKI.
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DOI：
10.1097/01.asn.0000074239.22357.06
发表时间：
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