The Effect of FR167653, p38 Mitogen-Activated Protein Kinase (MAPK) Inhibitor, on the Expression of Slit Diaphragm-Associated Proteins in Experimental Diabetic Nephropathy / 대한신장학회지
Korean Journal of Nephrology
; : 280-289, 2008.
Artigo
em Coreano
| WPRIM (Pacífico Ocidental)
| ID: wpr-184046
Biblioteca responsável:
WPRO
ABSTRACT
PURPOSE:
This study was undertaken to investigate the effect of a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor, FR167653, on urinary albumin excretion and on the expression of slit diaphragm-associated proteins in diabetic rats.METHODS:
Thirty-two Sprague-Dawley rats were injected with diluent [control (C), N=16] or streptozotocin intraperitoneally (DM, N=16). Eight rats from each group were treated with 5 mg/kg/day FR 167653 (C+FR, DM+FR) for 6 weeks. At the time of sacrifice, 24-hour urinary albumin excretion was determined by ELISA. Glomerular nephrin, P-cadherin, and ZO-1 mRNA and protein expression were determined by real-time PCR and Western blot, respectively, with sieved glomeruli.RESULTS:
Urinary albumin excretion was significantly higher in DM compared to C rats, and this increase in albuminuria was significantly inhibited by the administration of FR167653 in DM rats. Glomerular phospho-p38 MAPK protein expression was significantly increased in DM rats compared to C rats, and FR167653 treatment significantly attenuated the increase in phospho-p38 MAPK expression in DM glomeruli. Nephrin mRNA and protein expression were higher in 6-week DM compared to C glomeruli, and these increases were significantly abrogated with FR167653 treatment in DM rats. In contrast, FR167653 had no effects on the decrease in P-cadherin expression and the increase in ZO-1 expression observed in DM glomeruli.CONCLUSION:
These findings suggest that FR167653, a p38 MAPK inhibitor, reduce the amount of albuminuria in early diabetic nephropathy, and this anti-proteinuric effect seems to be related with the change of glomerular nephrin expression.
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Proteínas Quinases
/
Pirazóis
/
Piridinas
/
RNA Mensageiro
/
Ensaio de Imunoadsorção Enzimática
/
Proteínas
/
Caderinas
/
Western Blotting
/
Ratos Sprague-Dawley
/
Estreptozocina
Limite:
Animais
Idioma:
Coreano
Revista:
Korean Journal of Nephrology
Ano de publicação:
2008
Tipo de documento:
Artigo