Author:
Ding Chenguang,Zheng Jin,Wang Bo,Li Yang,Xiang Heli,Dou Meng,Qiao Yuxi,Tian Puxun,Ding Xiaoming,Xue Wujun
Abstract
Tubular epithelial cells (TECs) represent the primary site of renal ischemia/reperfusion injury (RIRI). However, whether the damage of TECs could drive the initiation of inflammation was unclear. Here we investigated the role of the TECs and macrophages during RIRI. Increased expression of inflammation response and activated M1 macrophage were determined in the mice model of RIRI. Moreover, we demonstrated global miRNA expression profiling of renal exosomes, and miR-374b-5p was most upregulated in these exosomes in vivo. Inhibition of miR-374b-5p in the mice upon RIR operation would alleviate the kidney injury via decreasing the production of proinflammatory cytokines and suppressing the macrophage activation. Similar results were also identified in the hypoxia-induced cell model where exosomal miR-374b-5p was dramatically upregulated. Uptake of exosomes derived from the hypoxic TECs by macrophages would trigger M1 polarization via transferring miR-374b-5p. Besides, we confirmed that miR-374b-5p could directly bind to Socs1 using a dual-luciferase reporter assay. Notably, when we injected the miR-374b-5p-enriched exosomes into mice, a high-level inflammatory response and M1 macrophage activation were performed. Our studies demonstrated that exosomal miR-374b-5p played an essential role in the communication between injured TECs and macrophages, resulting in the M1 macrophage activation during RIRI. The blockage of the release of such exosomes may serve as a new therapeutic strategy for RIRI.
Funder
National Natural Science Foundation of China
Fundamental Research Funds for the Central Universities
Subject
Cell Biology,Developmental Biology
Cited by
32 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献