NODding off in acute kidney injury with progranulin? Raghu K. Tadagavadi, W. Brian Reeves  Kidney International  Volume 87, Issue 5, Pages 873-875 (May 2015) DOI: 10.1038/ki.2015.14 Copyright © 2015 International Society of Nephrology Terms and Conditions

Figure 1 A hypothetical schema of PGRN function in AKI. Toxic or ischemic insults stimulate renal epithelial cells to produce proinflammatory mediators of tissue injury including damage-associated molecular patterns (DAMPs) and cytokines. The cytokines secreted by epithelial cells and infiltrated immune cells activate nuclear factor-κB (NF-κB) signaling and incite a cascade of inflammation characterized by the production of further cytokines and chemokines and upregulation of NOD2, a DAMP recognition receptor. Tumor necrosis factor (TNF) produced during kidney injury binds to TNF receptors and activates NF-κB signaling. PGRN can bind to TNF receptor and inhibit TNF signaling. PGRN is constitutively expressed by renal epithelial cells and also found abundantly in serum. In AKI, PGRN protects kidneys from renal tubular injury and attenuates production of inflammatory cytokines and chemokines and infiltration of leukocytes, possibly by inhibiting TNF receptor-mediated NF-κB activation and NOD2 induction. In addition, PGRN may cause activation and proliferation of T regulatory (Treg) cells with subsequent protection from AKI. Kidney International 2015 87, 873-875DOI: (10.1038/ki.2015.14) Copyright © 2015 International Society of Nephrology Terms and Conditions