title: The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/reperfusion-induced acute kidney injury.
abstract: Acute kidney injury (AKI) is a critical condition with a mortality rate as high as 50% and significantly contributes to the burden of end-stage renal disease (ESRD) requiring renal replacement therapy. The incidence and prognosis of AKI have been shown to vary with patient age, with younger individuals being more resistant to AKI. In mice, clamping the renal artery for 45 min causes substantial kidney damage in 4-month-old animals but only mild renal injury in 2-month-old animals. Here, younger mice were found to express higher levels of the NAD(+)-dependent histone deacetylase SIRT1 in the kidney. A small molecule SIRT1 activator, SRT-1720, markedly improved renal tubular pathology and overall renal function in adult mice following ischemia/reperfusion. Genetic ablation of one allele (SIRT1(+/-)) significantly enhanced the level of kidney damage relative to that in wild-type (SIRT1(+/+)) mice. The mechanisms underlying the protective effect of SIRT1 included the suppression of cell apoptosis. Hence, our results suggest that SIRT1 might be a novel therapeutic target for ischemia/reperfusion-induced kidney damage.
authors.affiliation: Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Fan
authors.forename: Hai-Chun
authors.initials: HC
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: You
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Wang
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: He
authors.forename: Chuan-Ming
authors.initials: CM
authors.lastname: Hao
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology*; D000818:Animals; D017209:Apoptosis; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D015427:Reperfusion Injury / Q000150:complications*; D056564:Sirtuin 1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; C525422:SRT1720; D016159:Tumor Suppressor Protein p53; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1