| First Author | Rong S | Year | 2014 |
| Journal | Am J Physiol Renal Physiol | Volume | 307 |
| Issue | 6 | Pages | F718-26 |
| PubMed ID | 25056349 | Mgi Jnum | J:214845 |
| Mgi Id | MGI:5604071 | Doi | 10.1152/ajprenal.00372.2013 |
| Citation | Rong S, et al. (2014) Renal PKC-epsilon deficiency attenuates acute kidney injury and ischemic allograft injury via TNF-alpha-dependent inhibition of apoptosis and inflammation. Am J Physiol Renal Physiol 307(6):F718-26 |
| abstractText | Acute kidney injury (AKI) increases the risk of morbidity and mortality after major surgery and transplantation. We investigated the effect of PKC-epsilon deficiency on AKI and ischemic allograft damage after kidney transplantation. PKC-epsilon-deficient and wild type (WT) control mice were subjected to 35 min of renal pedicle clamping to induce AKI. PKC-epsilon deficiency was associated with a marked improvement in survival and an attenuated loss of kidney function. Furthermore, functional MRI experiments revealed better renal perfusion in PKC-epsilon-deficient mice than in WT mice one day after IRI. Acute tubular necrosis and neutrophil infiltration were markedly reduced in PKC-epsilon-deficient mice. To determine whether this resistance to ischemia-reperfusion injury resulted from changes in local renal cells or infiltrating leukocytes, we studied a life-supporting renal transplant model of ischemic graft injury. We transplanted kidneys from H(2b) PKC-epsilon-deficient mice (129/SV) and their corresponding WT littermates into major histocompatibility complex-incompatible H(2d) recipients (BALB/c) and induced ischemic graft injury by prolonged cold ischemia time. Recipients of WT allografts developed severe renal failure and died within 10 days of transplantation. Recipients of PKC-epsilon-deficient allografts had better renal function and survival; they had less generation of ROS and upregulation of proinflammatory proteins (i.e., ICAM-1, inducible nitric oxide synthase, and TNF-alpha) and showed less tubular epithelial cell apoptosis and inflammation in their allografts. These data suggest that local renal PKC-epsilon expression mediates proapoptotic and proinflammatory signaling and that an inhibitor of PKC-epsilon signaling could be used to prevent hypoxia-induced AKI. |
