SIRT3 Alleviates LPS-Induced Acute Kidney Injury through Notch1 Signaling

Background: Acute kidney injury (AKI) is the main complication of critical care and has a variety of causes. Silent information regulator 2-related enzyme 3 (SIRT3) plays an important role in kidney diseases, including AKI. The aim of this study was to investigate the effect of SIRT3 on AKI in mice and its possible mechanism. Methods: Lipopolysaccharide (LPS) treatment was used to establish an animal model of AKI. Stable overexpression of SIRT3 in this model was achieved by injection of adeno-associated vector (Aav) expression system for overexpression of SIRT3 (AavSIRT3). Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were detected by biochemical analysis. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to evaluate SIRT3 and neurogenic locus notch homolog protein 1 (Notch1) expression levels. Enzyme-linked immunosorbent assay (ELISA) was used to quantify interleukin-1beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels, as well as oxidative stress indices. Western blot was used to evaluate the level of protein expression. Results: The LPS treatment group showed increased SCr, BUN, IL-1 beta, TNF-alpha, IL-6, malondialdehyde (MDA), and Notch1 compared to the control group, while the superoxide dismutase (SOD) level and SIRT3 expression were decreased. However, overexpression of SIRT3 could reverse the above changes. Similar changes in the levels of IL-1 beta, TNF-alpha, IL-6, MDA, SOD, Notch1 and hairy and enhancer of split-1 (Hes-1) were observed after SIRT3 overexpression in LPS-induced HK-2 cells. These changes could be reversed by the addition of Notch1 activator. Conclusions: SIRT3 can improve LPS-induced AKI by regulating Notch1 signaling, thus providing a new approach for the treatment of AKI.