Adenosine mediates transforming growth factor-beta 1 release in kidney glomeruli of diabetic rats

Abstract

Up regulation of the transforming growth factor-beta 1 (TGF-beta 1) 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 A(2B) receptor subtype (A(2B)AR) mediates TGF-beta 1 release from glomeruli of diabetic rats, a pathogenic event that could support progression of glomerulopathy when the bioavailability of adenosine is increased. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.