title: The Differential Effect of Apyrase Treatment and hCD39 Overexpression on Chronic Renal Fibrosis After Ischemia-Reperfusion Injury.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 1 Immunology Research Centre, St Vincent's Hospital, Melbourne, Victoria, Australia. 2 University of Melbourne, Victoria, Australia. 3 St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia. 4 School of Medicine, Faculty of Health, Deakin University, Victoria, Australia.
authors.forename: Veena
authors.initials: V
authors.lastname: Roberts
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Campbell
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
authors.forename: Joanne
authors.initials: J
authors.lastname: Chia
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cowan
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dwyer
mesh_terms: D058186:Acute Kidney Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001081:Apyrase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D002908:Chronic Disease; D004195:Disease Models, Animal; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005355:Fibrosis; D020022:Genetic Predisposition to Disease; D006801:Humans; D006868:Hydrolysis; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D000227:Adenine Nucleotides; D015703:Antigens, CD; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D001081:Apyrase; C067869:CD39 antigen