Adenosine A(2B) receptor-mediated VEGF induction promotes diabetic glomerulopathy

作者：Cardenas Angel; Toledo Camilo; Oyarzun Carlos; Sepulveda Angelica; Quezada Claudia; Guillen Gomez Elena; Diaz Encarnacion Montserrat M; Pastor Anglada Marcal; San Martin Rody^*

来源：Laboratory Investigation, 2013, 93(1): 135-144.

DOI：10.1038/labinvest.2012.143

• adenosine receptors
• diabetic nephropathy
• glomerulus
• VEGF

Diabetic nephropathy ranks as the most devastating kidney disease worldwide. It characterizes in the early onset by glomerular hypertrophy, hyperfiltration and mesangial expansion. Experimental models show that overproduction of vascular endothelial growth factor (VEGF) is a pathogenic condition for podocytopathy; however the mechanisms that regulate this growth factor induction are not clearly identified. We determined that the adenosine A(2B) receptor (A(2B)AR) mediates VEGF overproduction in ex vivo glomeruli exposed to high glucose concentration, requiring PKC alpha and Erk1/2 activation. The glomerular content of A(2B)AR was concomitantly increased with VEGF at early stages of renal disease in streptozotocin-induced diabetic rats. Further, in vivo administration of an antagonist of A(2B)AR in diabetic rats blocked the glomerular overexpression of VEGF, mesangial cells activation and proteinuria. In addition, we also determined that the accumulation of extracellular adenosine occurs in glomeruli of diabetic rats. Correspondingly, raised urinary adenosine levels were found in diabetic rats. In conclusion, we evidenced that adenosine signaling at the onset of diabetic kidney disease is a pathogenic event that promotes VEGF induction. Laboratory Investigation (2013) 93, 135-144; doi:10.1038/labinvest.2012.143; published online 15 October 2012

• 出版日期2013-1