Notch2/Hes-1 pathway plays an important role in renal ischemia and reperfusion injury-associated inflammation and apoptosis and the γ-secretase inhibitor DAPT has a nephroprotective effect.
Ren Fail
; 33(2): 207-16, 2011.
Article
en En
| MEDLINE
| ID: mdl-21332343
ABSTRACT
UNLABELLED This study aims to investigate the role of Notch pathway in the renal ischemia/reperfusion injury (IRI)-associated inflammation and apoptosis. MATERIALS AND METHODS:
Male Sprague-Dawley rats were divided into three groups normal saline (NS)-treated sham rats, NS-treated ischemia/reperfusion (I/R) rats, and N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT) (a γ-secretase inhibitor) treated I/R rats. I/R rat model underwent nephrectomy of the right kidney and was subjected to 60 min of left renal pedicle occlusion followed by 24 h, 48 h, and 72 h of reperfusion, respectively. The levels of creatinine, urea nitrogen (BUN), interleukin (IL)-6, tumor necrosis factor (TNF)-α in serum samples and urinary N-acety-ß-d-glucosaminidase (NAG) were assayed. Histological examinations were performed. The protein expression of Notch2, hairy/enhancer of split 1 (hes-1), NF-κB2, monocyte chemoattractant protein (MCP)-1, B-cell lymphoma 2 (bcl-2), and bcl-2-associated X (bax) were detected and the degree of apoptosis of tubular cells was evaluated.RESULTS:
Renal IR induced severe tubular damage, caused significant increases in the Scr, BUN, IL-6, TNF-α, urinary NAG, Notch2, hes-1, NF-κB2, MCP-1, ratio of tubule cells apoptosis, and reduction in the ratio of bcl-2 to bax. However, DAPT treatment significantly reduced the level of Scr, BUN, IL-6, TNF-α, and NAG. Thus, I/R activates Notch2/hes-1 signaling and DAPT treatment can ameliorate the severity of tubular damage after renal IRI, lower the expression of NF-κB2, MCP-1, and bax protein, increase the expression of bcl-2 protein, and reduce the ratio of terminal 2-deoxyuridine 5-triphosphate nick end-labeling-positive cells.CONCLUSION:
Notch signaling plays an important role in the renal IRI-associated inflammation and apoptosis. DAPT can protect against IRI through partly suppressing inflammation and apoptosis, which could constitute a new target for AKI.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_cardiovascular_diseases
/
6_kidney_renal_pelvis_ureter_cancer
Asunto principal:
Daño por Reperfusión
/
Proteínas de Homeodominio
/
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
/
Receptor Notch2
/
Secretasas de la Proteína Precursora del Amiloide
/
Lesión Renal Aguda
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Ren Fail
Asunto de la revista:
NEFROLOGIA
Año:
2011
Tipo del documento:
Article