Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Jun;9(2):135-43.
doi: 10.1007/s11302-012-9342-3. Epub 2012 Nov 29.

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

Veena Roberts  1 , Bo Lu, Siddharth Rajakumar, Peter J Cowan, Karen M Dwyer
Affiliations
Review

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

Veena Roberts et al. Purinergic Signal. 2013 Jun.

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Mechanism of protection by adenosine in renal IRI. In IRI, ATP is released from inflammatory and apoptotic cells via connexin and pannexin hemi-channels (blue rectangle) or directly from necrotic cells into the extracellular space. ATP is converted through an enzymatic process by CD39 and CD73 on endothelial cells (EC) to adenosine (ADO), increasing its extracellular concentration ([ADO]hi). Under hypoxic conditions, CD39 is upregulated by hypoxia-inducible specificity protein 1 (Sp1) and CD73 by hypoxia-inducible factor (HIF). Adenosine mediates its anti-inflammatory effects (brown broken arrows) via A1R on proximal tubule cells (PTC), A2AR on T regulatory cells (Treg) and A2BR on endothelial cells (EC). Adenosine itself increases the expression of CD73 (single green broken arrow). During ischemia, hypoxia-inducible factor is activated which inhibits transcription of equilibrative nucleoside transporter 1 (ENT1) enabling adenosine to remain in the extracellular space. HIF also increases the expression of A1R and A2BR. Sphingosine kinase-1 (SK1) and sphingosine-1-phosphate receptors (S1P1R) in the PTC augment the adenosine–A1R interaction. In the Treg, A2AR activation increases the expression of protein programmed-death 1(PD-1) which suppresses innate immune responses
See this image and copyright information in PMC

References

    1. Lohman AW, Billaud M, Isakson BE. Mechanisms of ATP release and signalling in the blood vessel wall. Cardiovasc Res. 2012;95(3):269–280. doi: 10.1093/cvr/cvs187. - DOI - PMC - PubMed
    1. Burnstock G. Purine and pyrimidine receptors. Cell Mol Life Sci. 2007;64(12):1471–1483. doi: 10.1007/s00018-007-6497-0. - DOI - PMC - PubMed
    1. Peng W, Cotrina ML, Han X, Yu H, Bekar L, Blum L, et al. Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury. Proc Natl Acad Sci USA. 2009;106(30):12489–12493. doi: 10.1073/pnas.0902531106. - DOI - PMC - PubMed
    1. Riegel A-K, Faigle M, Zug S, Rosenberger P, Robaye B, Boeynaems J-M, et al. Selective induction of endothelial P2Y6 nucleotide receptor promotes vascular inflammation. Blood. 2011;117(8):2548–2555. doi: 10.1182/blood-2010-10-313957. - DOI - PMC - PubMed
    1. McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CC, et al. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science. 2010;330(6002):362–366. doi: 10.1126/science.1195491. - DOI - PubMed

Publication types