Protective function of exosomes from adipose tissue-derived mesenchymal stem cells in acute kidney injury through SIRT1 pathway

Aims: To investigate the protective function of exosomes from adipose tissue-derived mesenchymal stem cells (AMSCs) in sepsis-induced acute kidney injury (AKI) in mice and the possible underlying mechanism in order to provide a theoretical and experimental basis for using exosomes in clinical. Main methods: The AKI model was prepared through cecal ligation and puncture (CLP). Exosomes were injected via the tail vein of mice. Male C57/BL6 mice (18-22 g; 6-8 weeks old) were randomly grouped. Firstly, after mice were modeled, the variations of inflammatory cytokines and kidney functions at different time points (0, 6, 12, 24 and 48 h) were comprehended. Secondly, mice were divided into Sham, CLP and CLP + Exo, and the survival rates of each group were observed. Lastly, a time point (24 h) was selected for exploring the effect and mechanism of exosomes. The levels of inflammatory cytokines in serum were detected by ELISA, while the kidney was by immunohistochemistry. Kidney histopathological score were analyzed by hematoxylin-eosin (HE) staining. The protein levels of sirtuin 1 (SIRT1), inflammation-related and apoptosis-related were detected by western blot. Key findings: In CLP group, renal function gradually deteriorated, and the kidneys was in a state of inflammation, apoptosis and microcirculation disorders. However, SIRT1 was activated after intervention of exosomes in CLP mice, which reversed above changes. The mortality was reduced with treatment of exosomes in AKI mice. Significance: In mice of sepsis-induce AKI, the intervention of AMSCs derived exosomes played a renal protective effect. The mechanism may be through SIRT1 signaling pathway.