Nox2 is a mediator of ischemia reperfusion injury.
Am J Transplant
; 15(11): 2888-99, 2015 Nov.
Article
en En
| MEDLINE
| ID: mdl-26104383
ABSTRACT
Delayed graft function (DGF) results from ischemia-reperfusion injury (IRI) and the generation of reactive oxygen species. We hypothesized that NADPH oxidase 2 (Nox2) plays an important role in pathways leading to DGF. We tested this hypothesis in vitro, in an animal model of IRI using wild type and Nox2(-/-) mice, and in patients with DGF. Under hypoxic conditions, primary tubular epithelial cells from Nox2(-/-) mice had reduced expression of MMP2, vimentin, and HSP27. BUN and creatinine levels were significantly increased in both Nox2(-/-) and WT mice at 4 weeks and 6 months after IRI, suggesting the development of acute and chronic kidney injury. At 4 weeks, kidney fibrosis (α-SMA, picrosirius) and oxidative stress (dihydroethidine, HNE) were significantly reduced in Nox2(-/-) mice, confirming the oxidative and pro-fibrotic effects of Nox2. The molecular signature of IRI using genomic analyses demonstrated a significant decline in hypoxia reponse, oxidative stress, fibrosis, and inflammation in Nox2(-/-) mice. Immunohistochemical analyses of pre-implanatation kidney allograft biopsies from patients with subsequent DGF showed significantly greater Nox2 levels and vascular injury compared with patients without DGF. These studies demonstrate that Nox2 is a modulator of IRI and its absence is associated with reduced inflammation, OS, and fibrosis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glicoproteínas de Membrana
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Daño por Reperfusión
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Trasplante de Riñón
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NADPH Oxidasas
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ARN Interferente Pequeño
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Funcionamiento Retardado del Injerto
Tipo de estudio:
Clinical_trials
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Observational_studies
/
Risk_factors_studies
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Am J Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2015
Tipo del documento:
Article