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Protective function of exosomes from adipose tissue-derived mesenchymal stem cells in acute kidney injury through
Fang Gao1, Bangjie Zuo2, Yanping Wang2
1Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
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.
Insights
Adipose tissue-derived mesenchymal stem cell exosomes protect against sepsis-induced acute kidney injury (AKI) in mice. This protective effect is mediated by activating the SIRT1 signaling pathway, offering a potential clinical treatment for AKI.
Area of Science:
- Stem cell biology
- Renal physiology
- Sepsis research
Background:
- Sepsis-induced acute kidney injury (AKI) is a critical condition with high mortality.
- Current treatments for sepsis-AKI are limited, necessitating novel therapeutic strategies.
- Mesenchymal stem cells (MSCs) and their derived exosomes show promise in regenerative medicine.
Purpose of the Study:
- To investigate the therapeutic potential of exosomes derived from adipose tissue-derived mesenchymal stem cells (AMSCs) in a mouse model of sepsis-induced AKI.
- To elucidate the underlying protective mechanisms of AMSC-derived exosomes in sepsis-AKI.
- To establish a basis for the clinical application of exosomes in treating AKI.
Main Methods:
- An acute kidney injury model was established using cecal ligation and puncture (CLP) in male C57/BL6 mice.
- Mice were treated with exosomes via tail vein injection and divided into Sham, CLP, and CLP + Exo groups.
- Kidney function, inflammatory cytokine levels, histopathology, apoptosis, and SIRT1 protein expression were assessed.
Main Results:
- Sepsis-induced AKI led to renal dysfunction, inflammation, apoptosis, and microcirculatory disturbances.
- Treatment with AMSC-derived exosomes significantly improved renal function and reduced mortality in CLP mice.
- Exosome intervention activated the SIRT1 signaling pathway, reversing the pathological changes associated with sepsis-AKI.
Conclusions:
- AMSC-derived exosomes exert a significant renal protective effect in a mouse model of sepsis-induced AKI.
- The protective mechanism is likely mediated through the activation of the SIRT1 signaling pathway.
- These findings support the potential of AMSC-derived exosomes as a novel therapeutic agent for sepsis-AKI.
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