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The differential effect of apyrase treatment and hCD39 overexpression on chronic renal fibrosis after ischemia-reperfusion injury
journal contribution
posted on 2017-07-01, 00:00 authored by V Roberts, D J Campbell, B Lu, J Chia, P J Cowan, Karen DwyerKaren DwyerBACKGROUND: Renal ischemia-reperfusion injury (IRI) leads to acute kidney injury and renal fibrosis. CD39 is a key purinergic enzyme in the hydrolysis of adenosine triphosphate (ATP) and increased CD39 enzymatic activity protects from acute IRI but its effect on renal fibrosis is not known. METHODS: Using a mouse model of unilateral renal IRI, the effects of increased CD39 activity (using soluble apyrase and mice expressing human CD39 transgene) on acute and chronic renal outcomes were examined. Nucleotide (ATP, adenosine diphosphate, adenosine monophosphate) and nucleoside (adenosine and inosine) levels were quantified by high-performance liquid chromatography. Soluble apyrase reduced acute renal injury at 24 hours and renal fibrosis at 4 weeks post-IRI, compared with vehicle-treated mice. RESULTS: Soluble apyrase reduced renal ATP, adenosine diphosphate, and adenosine monophosphate, but not adenosine levels, during ischemia. In comparison with wild-type littermates, hCD39 transgenic mice were protected from acute renal injury at 24 hours, but had increased renal fibrosis at 4 weeks post-IRI. hCD39 transgene expression was localized to the vascular endothelium at baseline and did not affect total renal nucleotide and nucleoside levels during ischemia. However, hCD39 transgene was more widespread at 4 weeks post-IRI and was associated with higher renal adenosine levels at 4 weeks post-IRI compared with wild-type littermates. CONCLUSIONS: A single dose of apyrase administration before IRI protects from both acute and chronic renal injuries and may have clinical application in protection from ischemic-induced renal injury. Furthermore, transgenic expression of hCD39 is associated with increased renal fibrosis after ischemia.
History
Journal
TransplantationVolume
101Issue
7Pagination
e194 - e204Publisher
Lippincott Williams & WilkinsLocation
Philadelphia, Pa.Publisher DOI
ISSN
0041-1337eISSN
1534-6080Language
engPublication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2017, Wolters Kluwer HealthUsage metrics
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No categories selectedKeywords
Acute Kidney InjuryAdenine NucleotidesAnimalsAntigens, CDApyraseChronic DiseaseDisease Models, AnimalEnzyme InductionEnzyme InhibitorsFibrosisGenetic Predisposition to DiseaseHumansHydrolysisKidneyMaleMice, Inbred C57BLMice, TransgenicPhenotypeRNA, MessengerReceptors, Adrenergic, beta-2Reperfusion InjuryTime FactorsScience & TechnologyLife Sciences & BiomedicineImmunologySurgeryTransplantationADENOSINE RECEPTORSDISEASEINFLAMMATIONINDUCTIONCD39MORTALITYNUCLEOTIDESPROTECTION
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