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Nitrosporeusine A attenuates sepsis-associated acute kidney injury through the downregulation of IL-6/sIL-6R axis activation-mediated PGC-1α suppression.

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Zhao Y,Nie M,Xu P,Li H,Xu L,Cheng XQ,Lei YQ

doi

10.1016/j.bbrc.2019.05.151

subject

Has Abstract

pub_date

2019-07-30 00:00:00

pages

474-480

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(19)31047-2

journal_volume

515

pub_type

杂志文章

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