title: Sirt1 deletion leads to enhanced inflammation and aggravates endotoxin-induced acute kidney injury.
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.
authors.affiliation: 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.
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.affiliation: Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Division of Cardiovascular Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Graduate Center for Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Shuxia
authors.initials: S
authors.lastname: Wang
authors.affiliation: Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
authors.forename: Sreerama
authors.initials: S
authors.lastname: Shetty
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Fu
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004731:Endotoxins / Q000009:adverse effects; D017353:Gene Deletion; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007684:Kidney Tubules / Q000473:pathology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D056564:Sirtuin 1