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Novel signalling mechanisms and targets in renal ischaemia and reperfusion injury

Item Type:Review
Title:Novel signalling mechanisms and targets in renal ischaemia and reperfusion injury
Creators Name:Kusch, A. and Hoff, U. and Bubalo, G. and Zhu, Y. and Fechner, M. and Schmidt-Ullrich, R. and Marko, L. and Müller, D.N. and Schmidt-Ott, K.M. and Gürgen, D. and Blum, M. and Schunck, W.H. and Dragun, D.
Abstract:Acute kidney injury (AKI) induced by ischaemia and reperfusion (I/R) injury is a common and severe clinical problem. Vascular dysfunction, immune system activation, and tubular epithelial cell injury contribute to functional and structural deterioration. The search for novel therapeutic interventions for I/R induced AKI is a dynamic area of experimental research. Pharmacologic targeting of injury mediators and corresponding intracellular signalling in endothelial cells, inflammatory cells and the injured tubular epithelium could provide new opportunities yet may also pose great translational challenge. Here, we focus on signalling mediators, their receptors and intracellular signalling pathways which bear potential to abrogate cellular processes involved in the pathogenesis of I/R induced AKI. Sphingosine 1 phosphate (S1P) and its respective receptors, cytochrome P450 (CYP450)-dependent vasoactive eicosanoids, NF-{kappa}B and protein kinase-C (PKC) related pathways are representatives of such "druggable" pleiotropic targets. For example pharmacologic agents targeting S1P and PKC isoforms are already in clinical use for treatment of autoimmune diseases and were previously subject of clinical trials in kidney transplantation where I/R induced AKI occurs as a common complication. We summarize recent in vitro and in vivo experimental studies using pharmacologic and genomic targeting and highlight some of the challenges to clinical application of these advances.
Keywords:Eicosanoids, Ischaemia, Kidney Reperfusion Injury, NF{kappa}B, PKC, Signal Transduction, Sphingosine 1-P, Animals
Source:Acta Physiologica
Page Range:25-40
Date:May 2013
Official Publication:https://doi.org/10.1111/apha.12089
PubMed:View item in PubMed

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