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Exosomes from miR-23 Overexpressing Stromal Cells Suppress M1 Macrophage and Inhibit Calcium Oxalate Deposition in
Zhang Yifan1, Zhang Shengli1, Wang Min1
1Department of Urology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, China.
Purpose:
To investigate whether ADSC-derived miR-23-enriched exosomes could protect against calcium oxalate stone formation in a hyperoxaluria rat model.
Methods:
An ethylene glycol- (EG-) induced hyperoxaluria rat model and an in vitro model of COM-induced HK-2 cells coculturing with RAW264.7 cells were established to explore the protective mechanisms of ADSC-derived miR-23-enriched exosomes.
Results:
The results showed that treatment with miR-23-enriched exosomes from ADSCs protected EG-induced hyperoxaluria rats, and cell experiments confirmed that coculturing with miR-23-enriched exosomes alleviated COM-induced cell autophagy. Overexpressed miR-23 suppressed M1 macrophage polarization by inhibiting IRF1 expression. Furthermore, the predicted binding site between the IRF1 messenger RNA 3'-untranslated region (3'-UTR) and miR-23 was confirmed by the dual-luciferase reporter assay.
Conclusion:
In conclusion, our research gave the first evidence that ADSC-derived miR-23-enriched exosomes affected the polarization of M1 macrophages by directly inhibiting IRF1 and protecting against calcium oxalate stone formation in a hyperoxaluria rat model.
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