Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Fletscherstrasse 74, 01307, Dresden, Germany.
Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Fletscherstrasse 74, 01307, Dresden, Germany.
Cell Chem Biol. 2020 Apr 16;27(4):448-462. doi: 10.1016/j.chembiol.2020.03.016.
In the last decade, the role of apoptosis in the pathophysiology of acute kidney injury (AKI) and AKI to chronic kidney disease (CKD) progression has been revisited as our understanding of ferroptosis and necroptosis has emerged. A growing body of evidence, reviewed here, ascribes a central pathophysiological role for ferroptosis and necroptosis to AKI, nephron loss, and acute tubular necrosis. We will introduce concepts to the non-cell-autonomous manner of kidney tubular injury during ferroptosis, a phenomenon that we refer to as a "wave of death." We hypothesize that necroptosis might initiate cell death propagation through ferroptosis. The remaining necrotic debris requires effective removal processes to prevent a secondary inflammatory response, referred to as necroinflammation. Open questions include the differences in the immunogenicity of ferroptosis and necroptosis, and the specificity of necrostatins and ferrostatins to therapeutically target these processes to prevent AKI-to-CKD progression and end-stage renal disease.
在过去的十年中，随着人们对铁死亡和坏死性凋亡的认识不断深入，细胞凋亡在急性肾损伤 (AKI) 病理生理学和 AKI 向慢性肾脏病 (CKD) 进展中的作用重新受到关注。在这里综述的越来越多的证据将铁死亡和坏死性凋亡的中心病理生理学作用归因于 AKI、肾单位丢失和急性肾小管坏死。我们将介绍铁死亡过程中肾小管损伤的非细胞自主方式的概念，我们将其称为“死亡波”。我们假设坏死性凋亡可能通过铁死亡引发细胞死亡的传播。剩余的坏死性碎片需要有效的清除过程来防止继发性炎症反应，称为坏死性炎症。目前仍存在一些悬而未决的问题，包括铁死亡和坏死性凋亡的免疫原性差异，以及坏死抑制剂和铁死亡抑制剂特异性靶向这些过程以预防 AKI 向 CKD 进展和终末期肾病的问题。
