Background Renal ischemia reperfusion injury (IRI) leads to delayed graft function (DGF) after kidney transplantion and contributes to acute transplant rejection as well as to progressive renal fibrosis. In this study we analysed the role of PKC-a in hypoxia induced impairment of renal blood flow (RBF) and edema formaion in PKC-a deficient mice compared to wildtype (WT) mice.
Methods IRI was induced in WT or PKC-a knock out mice by transient clamping of the renal pedicle for 35 min. Functional magnetic resonance imaging (MRI) was performed at d1 and d7 to measure renal blood flow (RBF), edema formation and cell infiltration. Histologically, renal morphology and inflammatory cell infiltration (F4/80 and GR-1 positive cells) were investigated. By qPCR PAI-1 and CTGF expression which are downstream targets of TGF-b were evaluated.
Results PKC-a 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-a knock out mice compared to WT mice at d1. Acute tubular necrosis (ATN) and inflammatory cell infiltration was significantly reduced in the PKC-a knock out mice. qPCR showed reduced up-regulation of PAI-1 in PKC-a deficient mice pointing towards impaired TGF-b signaling in this model.
Conclusion Our study proves that PKC-a deficiency attenuated hypoxia induced renal IRI by blocking TGF-b up-regulation. PKC-a deficiency results in improved renal tissue perfusion and less inflammation. Thus PKC-a inhibition might be a promising therapeutic option to reduce hypoxia induced IRI in solid organ transplantation.
To cite this abstract in AMA style:Walacides D, Rüskamp N, Song R, Hueper K, Mengel M, Meier M, Haller H, Schiffer M, Gueler F. Proteinkinase C Alpha Contributes to Impairment of Renal Blood Flow and Inflammation in Hypoxia Induced Renal Ischemia Reperfusion Injury (IRI) [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/proteinkinase-c-alpha-contributes-to-impairment-of-renal-blood-flow-and-inflammation-in-hypoxia-induced-renal-ischemia-reperfusion-injury-iri/. Accessed October 24, 2020.
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