| First Author | Li H | Year | 2018 |
| Journal | Am J Physiol Renal Physiol | Volume | 314 |
| Issue | 5 | Pages | F809-F819 |
| PubMed ID | 29357426 | Mgi Jnum | J:279733 |
| Mgi Id | MGI:6367454 | Doi | 10.1152/ajprenal.00569.2017 |
| Citation | Li H, et al. (2018) Divergent roles for kidney proximal tubule and granulocyte PAD4 in ischemic AKI. Am J Physiol Renal Physiol 314(5):F809-F819 |
| abstractText | We previously demonstrated that kidney peptidylarginine deiminase-4 (PAD4) plays a critical role in ischemic acute kidney injury (AKI) in mice by promoting renal tubular inflammation and neutrophil infiltration (Ham A, Rabadi M, Kim M, Brown KM, Ma Z, D'Agati V, Lee HT. Am J Physiol Renal Physiol 307: F1052-F1062, 2014). Although the role of PAD4 in granulocytes including neutrophils is well known, we surprisingly observed profound renal proximal tubular PAD4 induction after renal ischemia-reperfusion (I/R) injury. Here we tested the hypothesis that renal proximal tubular PAD4 rather than myeloid-cell lineage PAD4 plays a critical role in exacerbating ischemic AKI by utilizing mice lacking PAD4 in renal proximal tubules (PAD4(ff) PEPCK Cre mice) or in granulocytes (PAD4(ff) LysM Cre mice). Mice lacking renal proximal tubular PAD4 were significantly protected against ischemic AKI compared with wild-type (PAD4(ff)) mice. Surprisingly, mice lacking PAD4 in myeloid cells were also protected against renal I/R injury although this protection was less compared with renal proximal tubular PAD4-deficient mice. Renal proximal tubular PAD4-deficient mice had profoundly reduced renal tubular apoptosis, whereas myeloid-cell PAD4-deficient mice showed markedly reduced renal neutrophil infiltration. Taken together, our studies suggest that both renal proximal tubular PAD4 as well as myeloid-cell lineage PAD4 play a critical role in exacerbating ischemic AKI. Renal proximal tubular PAD4 appears to contribute to ischemic AKI by promoting renal tubular apoptosis, whereas myeloid-cell PAD4 is preferentially involved in promoting neutrophil infiltration to the kidney and inflammation after renal I/R. |
