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The CD39-adenosinergic axis in the pathogenesis of renal ischemia–reperfusion injury

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Abstract

Hypoxic injury occurs when the blood supply to an organ is interrupted; subsequent reperfusion halts ongoing ischemic damage but paradoxically leads to further inflammation. Together this is termed ischemia–reperfusion injury (IRI). IRI is inherent to organ transplantation and impacts both the short- and long-term outcomes of the transplanted organ. Activation of the purinergic signalling pathway is intrinsic to the pathogenesis of, and endogenous response to IRI. Therapies targeting the purinergic pathway in IRI are an attractive avenue for the improvement of transplant outcomes and the basis of ongoing research. This review aims to examine the role of adenosine receptor signalling and the ecto-nucleotidases, CD39 and CD73, in IRI, with a particular focus on renal IRI.

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Abbreviations

ADO:

Adenosine

ADP:

Adenosine diphosphate

AMP:

Adenosine monophosphate

ATP:

Adenosine triphosphate

cAMP:

3′-5′-Cyclic adenosine monophosphate

EC:

Endothelial cells

ENT1:

Equilibrative nucleoside transporter 1

HIF:

Hypoxia inducible factor

IP:

Ischemic preconditioning

IRI:

Ischemia–reperfusion injury

NPP:

Nucleotide pyrophosphatase/phosphodiesterase

PD-1:

Programmed death-1

PTC:

Proximal tubule cells

S1P1R:

Sphingosine-1-phosphate receptors

SK-1:

Sphingosine kinase-1

Treg:

Regulatory T cells

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Acknowledgments

Veena Roberts and Siddharth Rajakumar are supported by Kidney Health Australia, and Karen Dwyer is funded by Perpetual Philanthropic Services.

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Authors and Affiliations

  1. St. Vincent’s Hospital Melbourne, Immunology Research Centre, 41 Victoria Parade Fitzroy, 3065, Melbourne, Australia

    Veena Roberts, Bo Lu, Siddharth Rajakumar, Peter J. Cowan & Karen M. Dwyer

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  1. Veena Roberts
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  2. Bo Lu
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  3. Siddharth Rajakumar
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  4. Peter J. Cowan
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  5. Karen M. Dwyer
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Correspondence to Veena Roberts.

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Roberts, V., Lu, B., Rajakumar, S. et al. The CD39-adenosinergic axis in the pathogenesis of renal ischemia–reperfusion injury. Purinergic Signalling 9, 135–143 (2013). https://doi.org/10.1007/s11302-012-9342-3

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  • DOI: https://doi.org/10.1007/s11302-012-9342-3

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