Proteinkinase C Epsilon Contributes to Impairment of Renal Blood Flow and Inflammation in Renal Ischemia Reperfusion Injury (IRI)
Nephrology, Medical School Hannover, Hannover, Germany
Radiology, Medical School Hannover, Hannover, Germany
Applied Genomics Center, University of Alberta, Edmonton, Canada
Meeting: 2013 American Transplant Congress
Abstract number: D1573
Background – Proteinkinase C (PKC) isoforms are invovled in several signaling pathways contributing to ischemia reperfusion injury (IRI) and acute transplant rejection. Here we investigated PKC-e knock out mice in a clinically relavant model of hypoxia induced IRI leading acute renal failure with impairment of renal blood flow (RBF) and edema formation in wildtype mice.
Methods – IRI was induced by transient clamping of the renal pedicle for 35 min. Functional contrast free MRI was performed at d1 and d7 to measure renal blood flow (RBF), edema formation and cell infiltration. Histologically, acute tubular necrosis (ATN) and inflammatory cell infiltration (GR-1 and F4/80 positive cells) were investigated. TNF-alpha expression was examined by qPCR and immunohistochemistry.
Results – PKC-e knock out mice had significantly better survival and less s-creatinine elevation than WT mice. By MRI techniques IRI induced renal perfusion impairment was markedly reduced in PKC-e knock out mice compared to WT mice. Acute tubular necrosis (ATN) and inflammatory cell infiltration with Gr-1 pos cells was significantly reduced in the PKC-e knock out mice. qPCR and immunohistochemistry showed reduced up-regulation of TNF-a in PKC-e deficient mice.
Conclusion – Our study proves that PKC-e deficiency attenuated renal IRI by blocking TNF-a up-regulation and attenuating renal blood flow.
To cite this abstract in AMA style:
Rüskamp N, Walacides D, Song R, Hüper K, Mengel M, Meier M, Wacker D, Schiffer M, Haller H, Gueler F. Proteinkinase C Epsilon Contributes to Impairment of Renal Blood Flow and Inflammation in Renal Ischemia Reperfusion Injury (IRI) [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/proteinkinase-c-epsilon-contributes-to-impairment-of-renal-blood-flow-and-inflammation-in-renal-ischemia-reperfusion-injury-iri/. Accessed November 22, 2024.« Back to 2013 American Transplant Congress