Blocking TRAIL-DR5 signaling with soluble DR5 alleviates acute kidney injury in a severely burned mouse model.

Acute kidney injury (AKI) predicts high mortality in severely burned patients. Apoptosis plays a significant role during AKI; however, the apoptotic mechanisms underlying AKI induced by burn injury are not clear. Here, we report a critical role for tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-Death receptor 5 (DR5) signaling in the pathogenesis of AKI. C57BL/6 male mice were subjected to full thickness scald burn. Apoptosis was significantly up-regulated in mouse kidney 24 h after the burn. Meanwhile, the TRAIL and DR5 expression levels were significantly increased in the kidney 24 h after the burn. Soluble DR5 treatment reduced apoptotic cell death and alleviated kidney injury induced by the burn through blocking the interaction of endogenous TRAIL with DR5. These results demonstrated that TRAIL plays a deleterious role in AKI pathogenesis induced by scald burns. Inhibition of TRAIL function in the kidney may represent a novel protective strategy to treat AKI in patients with burns.