Adenosine A(2B) receptor mediates an increase on VEGF-A production in rat kidney glomeruli.
Up-regulation of the glomerular expression and the activity of vascular endothelial growth factor-A (VEGF) have been identified as an early pathogenic event for the progression of diabetic nephropathy. Currently, however the mediators are not yet clearly recognized. In this study we identified all four adenosine receptor (AR) subtypes, i.e. A(1), A(2A), A(2B) and A(3) in isolated rat kidney glomeruli. We localized the expression of A(2B)AR in podocytes, the primary VEGF producing cells. The ex vivo treatment of kidney glomeruli with adenosine or a general AR agonist NECA, increases VEGF protein content. In addition, NECA treatment elicits VEGF release. These effects were blocked by the A(2B)AR selective antagonist MRS1754 supplementation. Furthermore, we showed that A(2B)AR activation was necessary to promote a higher expression of VEGF in kidney glomeruli upon exposure to high d-glucose concentration, a pathogenic condition like those observed in diabetic nephropathy.
Laboratorio de Patología Molecular (LPM), Instituto de Bioquímica, Facultad de Ciencias, Universidad Austral de Chile, P.O. Box 567, Campus Isla Teja, Valdivia, Chile.
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Valladares
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Quezada
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Yañez
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Sobrevia
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San Martín
D000818:Animals; D002478:Cells, Cultured; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D043704:Receptor, Adenosine A2B; D042461:Vascular Endothelial Growth Factor A