Necroptosis mediated by receptor interaction protein kinase 1 and 3 aggravates chronic kidney injury of subtotal nephrectomised rats.

ABSTRACT

Necroptosis, an alternative mode of programmed cell death, has crucial pathophysiological roles in many diseases, but its effect on chronic kidney disease (CKD) is poorly understood. Therefore, we assessed necroptosis and its pathophysiological effects in a widely used remnant-kidney rat model. We found that necroptotic cell death and the highest level of receptor interaction protein kinase 1 (RIP1) and receptor interaction protein kinase 3 (RIP3), critical signalling molecules for necroptosis, appeared 8 weeks after subtotal nephrectomy (SNX) surgery. After treatment with Necrostatin-1 (Nec-1), renal function and renal pathologic changes were significantly improved; the overexpression of RIP1, RIP3, mixed lineage kinase domain-like (MLKL) and dynamin-related protein 1 (Drp1) was reduced; and necroptosis was inhibited. These results indicated that necroptosis mediated by RIP1 and RIP3 participates in the loss of renal cells of subtotal nephrectomised rats and might be one of main causes of the excessive loss of renal cells during the sustained progression of renal fibrosis.