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TWEAK and RIPK1 mediate a second wave of cell death during AKI

2018; National Academy of Sciences; Volume: 115; Issue: 16 Linguagem: Inglês

10.1073/pnas.1716578115

1091-6490

Diego Martín‐Sánchez, Miguel Fontecha‐Barriuso, Susana Carrasco, María Dolores Sánchez-Niño, Anne von Mäßenhausen, Andreas Linkermann, Pablo Cannata‐Ortiz, Marta Ruíz-Ortega, Jesús Egido, Alberto Ortíz, Ana B. Sanz,

Renal and related cancers

Significance Acute kidney injury (AKI) has a mortality of 50%. There is no satisfactory therapy and the incidence is increasing. The etiology of AKI is heterogeneous, and this has therapeutic implications. Here we show that necroptosis plays a role in a second wave of tubular cell death in experimental toxic AKI. This second wave of death is triggered by TWEAK activation of the Fn14 receptor and contributes to persistence of injury. We previously observed that the initial wave of cell death was ferroptosis dependent and necroptosis independent. The identification of a pathway contributing to AKI persistence may facilitate the design of therapies, as exemplified by the protection afforded by RIPK1 inhibitors when administered after AKI had been induced.