Deakin University
Browse
dwyer-transgenicoverexpression-2010.pdf (885.01 kB)

Transgenic overexpression of CD39 protects against renal ischemia-reperfusion and transplant vascular injury

Download (885.01 kB)
Version 2 2024-06-03, 18:14
Version 1 2019-03-08, 10:47
journal contribution
posted on 2024-06-03, 18:14 authored by S Crikis, B Lu, LM Murray-Segal, C Selan, SC Robson, AJF D'Apice, HH Nandurkar, PJ Cowan, KM Dwyer
The vascular ectonucleotidases CD39[ENTPD1 (ectonucleoside triphosphate diphosphohydrolase-1), EC 3.6.1.5] and CD73[EC 3.1.3.5] generate adenosine from extracellular nucleotides. CD39 activity is critical in determining the response to ischemia-reperfusion injury (IRI), and CD39 null mice exhibit heightened sensitivity to renal IRI. Adenosine has multiple mechanisms of action in the vasculature including direct endothelial protection, antiinflammatory and antithrombotic effects and is protective in several models of IRI. Mice transgenic for human CD39 (hCD39) have increased capacity to generate adenosine. We therefore hypothesized that hCD39 transgenic mice would be protected from renal IRI. The overexpression of hCD39 conferred protection in a model of warm renal IRI, with reduced histological injury, less apoptosis and preserved serum creatinine and urea levels. Benefit was abrogated by pretreatment with an adenosine A2A receptor antagonist. Adoptive transfer experiments showed that expression of hCD39 on either the vasculature or circulating cells mitigated IRI. Furthermore, hCD39 transgenic kidneys transplanted into syngeneic recipients after prolonged cold storage performed significantly better and exhibited less histological injury than wild-type control grafts. Thus, systemic or local strategies to promote adenosine generation and signaling may have beneficial effects on warm and cold renal IRI, with implications for therapeutic application in clinical renal transplantation.

History

Journal

American journal of transplantation

Volume

10

Pagination

2586-2595

Location

Chichester, Eng.

Open access

  • Yes

eISSN

1600-6143

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2010, The Authors

Issue

12

Publisher

John Wiley & Sons

Usage metrics

    Research Publications

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC