MICRORNA-223 IN MSCS-DERIVED EXOSOMES AMELIORATES RENAL ISCHEMIA/REPERFUSION INJURY BY INHIBITION PYROPTOSIS

Renal ischemia/reperfusion (I/R) injury is the main cause of acute kidney injury, renal failure, early functional recovery and long-term survival of transplanted kidney. However, the pathophysiological mechanism of renal I/R injury is very complicated and has not been fully elucidated. Mesenchymal stem cells (MSCs) therapy is a hotspot in the field of IR injury in recent years. Studies have shown that miRNAs in exosomes of MSCs play an important role in I/R injury. As an important member of the miRNA family, miR-223 has been studied as a tumor-associated gene in previous researches. With a deeper understanding of miR-223, it has been found to be closely related to I/R injury. In the study of myocardial I/R injury, it was found that the anti-apoptotic effect on myocardium is closely related to the increased expression of miR-223. These findings suggest that miR-223 may play a protective role in the kidneys through negative regulation of target genes in renal I/R injury. Therefore, we constructed a model of renal I/R injury in BALB/c mice to explore the regulation of miR-223 in renal I/R injury. The study found that miR-223 significantly reduced renal I/R injury compared with the model group. Importantly, western blot analysis showed that NLRP3 and caspase1 were significantly down-regulated after overexpression of miR-223, and the expression of inflammatory factors IL-18 and IL-1β was also significantly decreased. In addition, knockdown of miR-223 effectively attenuated the protective effect of exosomes on renal I/R injury. In conclusion, our results indicate that miR-223 in the exosomes negatively regulates the target gene NLPR3, blocking or reducing the pyroptosis of renal tissue cells and protecting the kidneys. This study not only confirmed the protective effect of MSCs on renal tissues but also explained the regulation mechanism of miR-223 in renal I/R injury. The National Natural Science Foundation of China (Nos. 81670681, 81760137, and 81870514). the grants from the Fundamental Research Funds for the Central Universities(No. xjj2018091). the Scientific and Technological Breakthrough in Social Development of Shaanxi Province (No. 2016SF-246). the Special Supportive Program for Organ Transplantation by COTDF. the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University (No. XJTU1AF-CRF-2019-008).