Adenosine A(2B) receptor-mediated VEGF induction promotes diabetic glomerulopathy.
Lab Invest
; 93(1): 135-44, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-23069939
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 PKCα 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator A de Crescimento do Endotélio Vascular
/
Receptor A2B de Adenosina
/
Diabetes Mellitus Experimental
/
Nefropatias Diabéticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Lab Invest
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Estados Unidos