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

作者：Chenguang Ding, Meng Dou, Yuxiang Wang, Yuxi Qiao, Ying Wang, Yang Li, Jin Zheng, Xiaoming Ding, Wujun Xue, Puxun Tian · 发表于：Transplantation · 年份：2020 · DOI：10.1097/01.tp.0000699208.26513.6b · 研究领域：Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Muscle and Compartmental Disorders、Dermatological and COVID-19 studies

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 pro...