Nitrosporeusine A attenuates sepsis-associated acute kidney injury through the downregulation of IL-6/sIL-6R axis activation-mediated PGC-1α suppression.
Biochem Biophys Res Commun
; 515(3): 474-480, 2019 07 30.
Article
em En
| MEDLINE
| ID: mdl-31164200
ABSTRACT
Nitrosporeusine A (NA) has been recently reported to exert anti-inflammatory and renal protective effects, but whether NA can attenuate sepsis-associated acute kidney injury (AKI) has not yet been reported. In this study, our results found that cecal ligation and puncture (CLP) reduced renal PGC-1α expression and induced oxidative stress in C57BL/6 mice. PGC-1α overexpression attenuated CLP-induced AKI with decreased oxidative stress, whereas worsened AKI with excessive reactive oxygen species (ROS) production was observed in renal specific PGC-1α knockout (NiPKO) mice. In addition, PGC-1α expression is retained in IL-6-/- mice and wild-type (WT) C57BL/6 mice received JAK2/STAT3 inhibition. Finally, administration of NA attenuated CLP-induced AKI with decreased IL-6/sIL-6R axis activation, increased PGC-1α expression, and diminished ROS production in injured kidneys. However, NA failed to attenuate CLP-induced AKI in NiPKO mice. Together, these results suggested that NA attenuates sepsis-associated AKI through the downregulation of IL-6/sIL-6R axis activation-mediated renal PGC-1α suppression.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação para Baixo
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Sepse
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Receptores de Interleucina-6
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Alcaloides
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Injúria Renal Aguda
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Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article