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Adenosine mediates transforming growth factor-beta 1 release in kidney glomeruli of diabetic rats
Authors:H Roa  E Troncoso  C Escudero  L Sobrevia  C Quezada
Institution:a Laboratorio Patología Molecular, Instituto de Bioquímica, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
b Cellular and Molecular Physiology Laboratory (CMPL) & Perinatology Research Laboratory (PRL), Department of Obstetrics and Gynaecology, Medical Research Center (CIM), School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
c Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina (IBUB), Universitat de Barcelona and CIBER EHD, Spain
Abstract:Up regulation of the transforming growth factor-beta 1 (TGF-β1) axis has been recognized as a pathogenic event for progression of glomerulosclerosis in diabetic nephropathy. We demonstrate that glomeruli isolated from diabetic rats accumulate up to sixfold more extracellular adenosine than normal rats. Both decreased nucleoside uptake activity by the equilibrative nucleoside transporter 1 and increased AMP hydrolysis contribute to raise extracellular adenosine. Ex vivo assays indicate that activation of the low affinity adenosine A2B receptor subtype (A2BAR) mediates TGF-β1 release from glomeruli of diabetic rats, a pathogenic event that could support progression of glomerulopathy when the bioavailability of adenosine is increased.
Keywords:Adenosine receptor  Transforming growth factor-beta 1  Diabetic nephropathy  Glomerulus
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