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.
Document Type
Article
Publication Date
5-4-2014
Digital Object Identifier (DOI)
http://dx.doi.org/10.1371/journal.pone.0098909
Repository Citation
Gao, Rong; Chen, Jiao; Hu, Yuxin; Li, Zhenyu; Wang, Shuxia; Shetty, Sreerama; and Fu, Jian, "Sirt1 Deletion Leads to Enhanced Inflammation and Aggravates Endotoxin-Induced Acute Kidney Injury" (2014). Toxicology and Cancer Biology Faculty Publications. 24.
https://uknowledge.uky.edu/toxicology_facpub/24
Notes/Citation Information
Published in PLOS One, v. 9, issue 6, e98909.
© 2014 Gao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.