Xu Yanfang, Han Jiahuai
Department of Nephrology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China.
Semin Nephrol. 2016 May;36(3):199-207. doi: 10.1016/j.semnephrol.2016.03.007.
Cell death and inflammation in the proximal tubules are the hallmarks of acute kidney injury (AKI), but the underlying mechanism has not been fully elucidated. Recent evidence has shown that necroptosis, a type of programmed necrosis, plays an important role in AKI. The necrosis-inducing signaling complex is called the necrosome, which contains receptor-interacting protein 1, receptor-interacting protein 3, and mixed lineage kinase domain-like protein. Studies have found that inhibition of the core components of the necroptotic pathway by gene knockout, RNA interference, or a chemical inhibitor diminished proximal tubule damage, showing that necroptosis is a major contributor to AKI. This review focuses on the functional roles of the necrosome in regulating renal tubular cell necroptosis, and the physiological and pathologic roles of necrosome in AKI.
近端肾小管中的细胞死亡和炎症是急性肾损伤（AKI）的标志，但其潜在机制尚未完全阐明。最近的证据表明，坏死性凋亡，一种程序性坏死，在急性肾损伤中起重要作用。诱导坏死的信号复合物称为坏死小体，它包含受体相互作用蛋白1、受体相互作用蛋白3和混合谱系激酶结构域样蛋白。研究发现，通过基因敲除、RNA干扰或化学抑制剂抑制坏死性凋亡途径的核心成分可减轻近端肾小管损伤，表明坏死性凋亡是急性肾损伤的主要原因。本综述重点关注坏死小体在调节肾小管细胞坏死性凋亡中的功能作用，以及坏死小体在急性肾损伤中的生理和病理作用。
