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Karsten Bartels, Almut Grenz, Holger K. Eltzschig  Kidney International 

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1 Sphingosine-1-phosphate receptor signaling during acute kidney injury: the tissue is the issue 
Karsten Bartels, Almut Grenz, Holger K. Eltzschig  Kidney International  Volume 85, Issue 4, Pages (April 2014) DOI: /ki Copyright © 2014 International Society of Nephrology Terms and Conditions

2 Figure 1 Effects of vascular endothelial and tubular sphingosine-1-phosphate 1 receptor signaling in ischemic acute kidney injury. Sphingosine-1-phosphate (S1P) is synthesized from the sphingolipids sphingosine, sphingomyelin, ceramide, and others. S1P synthesis is dependent on the activity of sphingosine kinases and S1P-selective phosphorylase, as they regulate phosphorylation of sphingosine to S1P. As a ligand for sphingosine-1-phosphate 1 receptor (S1P1R), S1P initiates various signaling pathways. Endothelial-specific S1P1R deletion is associated with increased renal tubular necrosis, inflammation, and impaired vascular permeability and exacerbates renal tubular apoptosis after ischemic acute kidney injury. One mechanism for the protective effects of endothelial S1P1R activation lies within the induction of heat-shock protein 27 (HSP27).3 In the proximal tubule, S1P1R activation leads to direct blockage of apoptosis and induction of cell survival via activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK)-induced and phosphatidylinositol-3-kinase (PI3K)/Akt-induced pathways.9 Kidney International  , DOI: ( /ki ) Copyright © 2014 International Society of Nephrology Terms and Conditions


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