Adenosine A(2B) receptor-mediated VEGF induction promotes diabetic glomerulopathy
Por:
Cardenas, A, Toledo, C, Oyarzun, C, Sepulveda, A, Quezada, C, Guillen-Gomez, E, Diaz-Encarnacion, MM, Pastor-Anglada, M, San Martin, R
Publicada:
1 ene 2013
Resumen:
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
Filiaciones:
Cardenas, A:
Univ Austral Chile, Fac Ciencias, Inst Bioquim & Microbiol, Lab Patol Mol, Valdivia 5110566, Chile
Toledo, C:
Univ Austral Chile, Fac Ciencias, Inst Bioquim & Microbiol, Lab Patol Mol, Valdivia 5110566, Chile
Oyarzun, C:
Univ Austral Chile, Fac Ciencias, Inst Bioquim & Microbiol, Lab Patol Mol, Valdivia 5110566, Chile
Sepulveda, A:
Univ Austral Chile, Fac Ciencias, Inst Bioquim & Microbiol, Lab Patol Mol, Valdivia 5110566, Chile
Quezada, C:
Univ Austral Chile, Fac Ciencias, Inst Bioquim & Microbiol, Lab Patol Mol, Valdivia 5110566, Chile
Guillen-Gomez, E:
Univ Autonoma Barcelona, Serv Nefrol, Fundacio Puigvert, REDinREN,FRIAT,Inst Invest Biosanit St Pau, Barcelona, Spain
Diaz-Encarnacion, MM:
Univ Autonoma Barcelona, Serv Nefrol, Fundacio Puigvert, REDinREN,FRIAT,Inst Invest Biosanit St Pau, Barcelona, Spain
Pastor-Anglada, M:
Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, Barcelona, Spain
San Martin, R:
Univ Austral Chile, Fac Ciencias, Inst Bioquim & Microbiol, Lab Patol Mol, Valdivia 5110566, Chile
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