Sirt1 deletion leads to enhanced inflammation and aggravates endotoxin-induced acute kidney injury

Rong Gao, Jiao Chen, Yuxin Hu, Zhenyu Li, Shuxia Wang, Sreerama Shetty, Jian Fu

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Bacterial endotoxin has been known to induce excessive inflammatory responses and acute kidney injury. In the present study, we used a mouse model of endotoxemia to investigate the role of Sirt1 in inflammatory kidney injury. We examined molecular and cellular responses in inducible Sirt1 knockout (Sirt1-/-) mice and wild type littermates (Sirt1+/+) in lipopolysaccharide (LPS)-induced kidney injury. Our studies demonstrated that Sirt1 deletion caused aggravated kidney injury, which was associated with increased inflammatory responses including elevated pro-inflammatory cytokine production, and increased ICAM-1 and VCAM-1 expression. Inflammatory signaling such as STAT3/ERK phosphorylation and NF-κB activation was markedly elevated in kidney tissues of Sirt1 knockout mice after LPS challenge. The results indicate that Sirt1 is protective against LPS-induced acute kidney injury by suppressing kidney inflammation and down-regulating inflammatory signaling.

Original languageEnglish
Article numbere98909
JournalPLoS ONE
Volume9
Issue number6
DOIs
StatePublished - Jun 4 2014

ASJC Scopus subject areas

  • General

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