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PLoS One. 2014 Jun 4;9(6):e98909. doi: 10.1371/journal.pone.0098909. eCollection 2014.

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

Author information

1
The Second Hospital of Jilin University, Changchun, Jilin, China; Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
2
Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
3
Division of Cardiovascular Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
4
Graduate Center for Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
5
Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
6
Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, Kentucky, United States of America; Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, Kentucky, United States of America.

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.

PMID:
24896770
PMCID:
PMC4045768
DOI:
10.1371/journal.pone.0098909
[Indexed for MEDLINE]
Free PMC Article
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