RAGE-aptamer attenuates deoxycorticosterone acetate/salt-induced renal injury in mice.
Sci Rep
; 8(1): 2686, 2018 02 08.
Article
em En
| MEDLINE
| ID: mdl-29422652
ABSTRACT
The mineralocorticoid receptor (MR) and its downstream signaling play an important role in hypertensive renal injury. The interaction of advanced glycation end products (AGE) with their receptor (RAGE) is involved in the progression of renal disease. However, the pathological crosstalk between AGE-RAGE axis and MR system in kidney derangement remains unclear. We screened DNA-aptamer directed against RAGE (RAGE-apt) in vitro and examined its effects on renal injury in uninephrectomized deoxycorticosterone acetate (DOCA)/salt-induced hypertensive mice. RAGE, GTP-bound Rac-1 (Rac1), and MR were co-localized in the podocytes of DOCA mice. The deletion of RAGE gene significantly inhibited mesangial matrix expansion and tubulointerstitial fibrosis in DOCA mice, which was associated with the reduction of glomerular oxidative stress, MR, Rac1, and urinary albumin excretion (UAE) levels. RAGE-apt attenuated the increase in carboxymethyllysine (CML), RAGE, nitrotyrosine, Rac1, and MR levels in the kidneys and reduced UAE in DOCA mice. Aldosterone (Aldo) increased nitrotyrosine, CML, and RAGE gene expression in murine podocytes, whereas CML stimulated MR and Rac1 levels, which were blocked by RAGE-apt. The present study indicates the crosstalk between the AGE-RAGE axis and Aldo-MR system, suggesting that RAGE-apt may be a novel therapeutic tool for the treatment of MR-associated renal diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aptâmeros de Peptídeos
/
Injúria Renal Aguda
/
Receptor para Produtos Finais de Glicação Avançada
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão