Pathophysiological role of different tubular epithelial cell death modes in acute kidney injury.
Pathophysiological role of different tubular epithelial cell death modes in acute kidney injury.
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DOI：
10.1093/ckj/sfv069
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发表时间：
2015-10
影响因子：
4.6
通讯作者：
López-Hernández FJ
中科院分区：
文献类型：
--
作者：
Sancho-Martínez SM;López-Novoa JM;López-Hernández FJ
许多形式的内源性急性肾损伤（阿基）的组织学基质通常归因于肾小管坏死。然而，最近的研究表明，坏死不是阿基中细胞死亡的主要形式，其他形式如细胞凋亡、调节性坏死（即坏死性凋亡和死亡）、自噬性细胞死亡和有丝分裂灾难也参与阿基，并且它们的贡献取决于阿基的原因和阶段。在此，我们简要总结了主要类型的细胞死亡的主要特征，我们还批判性地回顾了现有的证据，在阿基和人体标本的最常见的实验模型中报告的不同类型的细胞死亡的发生。我们还讨论了肾小管上皮细胞死亡与肾小球滤过减少、氮质血症和水电解质失衡的病理生理机制。例如，对某些形式的细胞死亡的炎性成分的分析作为重要的和不同的病理生理学决定因素，特别相关。最后，涉及每种细胞死亡类型的已知分子机制和信号传导途径提出了适当的靶点，以特异性预防或逆转阿基，前提是在不久的将来，对它们在每种阿基综合征中的参与和影响的进一步了解将逐步增加。
The histological substrate of many forms of intrinsic acute kidney injury (AKI) has been classically attributed to tubular necrosis. However, more recent studies indicate that necrosis is not the main form of cell death in AKI and that other forms such as apoptosis, regulated necrosis (i.e. necroptosis and parthanatos), autophagic cell death and mitotic catastrophe, also participate in AKI and that their contribution depends on the cause and stage of AKI. Herein, we briefly summarize the main characteristics of the major types of cell death and we also critically review the existing evidence on the occurrence of different types of cell death reported in the most common experimental models of AKI and human specimens. We also discuss the pathophysiological mechanisms linking tubule epithelial cell death with reduced glomerular filtration, azotaemia and hydroelectrolytic imbalance. For instance, special relevance is given to the analysis of the inflammatory component of some forms of cell death over that of others, as an important and differential pathophysiological determinant. Finally, known molecular mechanisms and signalling pathways involved in each cell death type pose appropriate targets to specifically prevent or reverse AKI, provided that further knowledge of their participation and repercussion in each AKI syndrome is progressively increased in the near future.