Renal NFκB essential modulator (NEMO) mediates ischemic acute kidney injury in mice

다국어 초록 (Multilingual Abstract)

We determined that renal proximal tubular NFκB essential modulator (NEMO) has a crucial role in ischemic acute kidney injury (AKI) using mice lacking renal proximal tubular NEMO and by targeted proximal tubular NEMO inhibition with mesoscale nanoparticle encapsulated NEMO binding peptide (MNP NBP). Mice were subjected to sham surgery or 30 min renal ischemia and reperfusion (IR). Mice deficient in proximal tubular NEMO and mice treated with MNP NBP were protected against ischemic AKI with decreased renal tubular necrosis, apoptosis and inflammation compared to those control mice. Treatment of recombinant peptidylarginine deiminase type-4 (rPAD4) aggravates ischemic AKI in WT mice but not in mice lacking renal proximal tubular NEMO. Furthermore, rPAD4 upregulated proinflammatory cytokine mRNA and NFκB activation in freshly isolated renal proximal tubules from WT mice but not from proximal tubule NEMO deficient mice. Taken together, our studies suggest that proximal tubular NEMO plays a critical role in ischemic AKI by promoting renal tubular inflammation, apoptosis as well as necrosis.