Podocyte NF ‐ κ B is dispensable for the pathogenesis of renal ischemia‐reperfusion injury

Podocytes play a central role in the formation of the glomerular filtration barrier in the kidney, and their dysfunction has been shown to result in multiple proteinuric kidney diseases. In this study, we sought to determine whether NF ‐ κ B, a proinflammatory signaling, within podocytes was involved in renal ischemia‐reperfusion (I/R) injury. Podocyte‐specific I κ BΔN transgenic (Pod‐I κ BΔN) mice, in which NF ‐ κ B was inhibited specifically in podocytes, were generated by the Cre‐loxP technology, and their phenotype was compared with control mice after bilateral renal ischemia. The effect of systemic administration of a NF ‐ κ B inhibitor, pyrrolidinedithiocarbamate ( PDTC ), on renal I/R injury was also examined. Pod‐I κ BΔN mice were phenotypically normal before surgery. Following renal I/R injury, serum concentrations of urea nitrogen and creatinine were elevated in both Pod‐I κ BΔN and control mice to a similar extent, whereas PDTC treatment attenuated the elevation of these parameters. Renal histological damage in I/R‐injured Pod‐I κ BΔN mice was also similar to I/R‐injured control mice, although it was improved by PDTC treatment. Moreover, I/R induced accumulation of inflammatory cells, such as neutrophils and macrophages, was reduced by PDTC treatment, but not by podocyte‐specific NF ‐ κ B inhibition. These results provide evidence that the NF ‐ κ B activity in podocytes does not contribute to the pathogenesis of renal I/R injury.