title: Adenosine A2 a receptor stimulation prevents proteinuria in diabetic rats by promoting an anti-inflammatory phenotype without affecting oxidative stress.
abstract: OBJECTIVE
  Diabetic patients are at increased risk for kidney disease. There is presently no clinical treatment available that effectively protects kidney function in diabetics. This study investigates whether chronic stimulation of the adenosine A2a receptor (A2a AR) protects kidney function in insulinopenic diabetic rats.
  
  
  METHODS
  Streptozotocin-induced diabetic rats and corresponding controls were chronically treated with the adenosine A2a AR agonist CGS21680 throughout the four-week diabetes duration. Kidney function was thereafter investigated, and urine and plasma samples were collected for analysis of protein, oxidative stress and inflammatory markers.
  
  
  RESULTS
  Glomerular filtration rate, renal blood flow, filtration fraction and diabetes-induced kidney hypoxia were all unaffected by chronic A2a AR stimulation. Furthermore, diabetic rats had increased oxidative stress, which was further increased by chronic A2a AR stimulation. However, the 10-fold increased urinary protein excretion observed in the diabetic rats was completely prevented by chronic A2a AR stimulation. These beneficial effects were accompanied by reduced levels of the pro-inflammatory TNF-α and increased levels of the anti-inflammatory IL-10 as well as decreased infiltration of macrophages, glomerular damage and basement membrane thickness.
  
  
  CONCLUSIONS
  Chronic A2a AR stimulation prevents proteinuria and glomerular damage in experimental diabetes via an anti-inflammatory mechanism independent of oxidative stress and kidney hypoxia.
authors.affiliation: Division of Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Persson
authors.affiliation: Division of Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Friederich-Persson
authors.affiliation: Division of Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Fasching
authors.affiliation: Division of Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hansell
authors.affiliation: Division of Chronic Kidney Disease Pathophysiology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Inagi
authors.affiliation: Division of Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.|Division of Drug Research, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.|Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Palm
mesh_terms: D000241:Adenosine; D000818:Animals; D016207:Cytokines / Q000276:immunology*; D003928:Diabetic Nephropathies / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D008297:Male; D018384:Oxidative Stress / Q000276:immunology*; D011507:Proteinuria / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000276:immunology*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D043705:Receptor, Adenosine A2A; D000241:Adenosine
keywords: CGS21680; diabetes mellitus; diabetic nephropathy; kidney; macrophages; tumour necrosis factor-alpha