Research Paper Volume 13, Issue 5 pp 6752—6764
Extracellular vesicle-encapsulated microRNA-23a from dorsal root ganglia neurons binds to A20 and promotes inflammatory macrophage polarization following peripheral nerve injury
- 1 Sichuan Medicine Key Laboratory of Clinical Genetics/Central Laboratory, Affiliated Hospital of Chengdu University, Chengdu 610081, P.R. China
- 2 Department of Pediatrics, Affiliated Hospital of Chengdu University, Chengdu 610081, P.R. China
- 3 Department of Neurology, Affiliated Hospital of Chengdu University, Chengdu 610081, P.R. China
Received: February 24, 2020 Accepted: September 24, 2020 Published: February 17, 2021https://doi.org/10.18632/aging.202532
How to Cite
Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Extracellular vesicles (EVs) are capable of transferring microRNAs (miRNAs or miRs) between two different types of cells and also serve as vehicles for delivery of therapeutic molecules. After peripheral nerve injury, abnormal expression patterns of miRNAs have been observed in dorsal root ganglia (DRG) sensory neurons. We hypothesized that sensory neurons secrete miRs-containing EVs to communicate with macrophages. We demonstrated that miR-23a was upregulated in DRG neurons in spared nerve injury (SNI) mouse models. We also found that miR-23a was enriched in EVs released by cultured DRG neurons following capsaicin treatment. miR-23a-containing EVs were taken up into macrophages in which increased intracellular miR-23a promoted pro-inflammatory phenotype. A20 was verified as a target gene of miR-23a. Moreover, intrathecal delivery of EVs-miR-23a antagomir attenuated neuropathic hypersensitivity and reduced the number of M1 macrophages in injured DRGs by targeting A20. In conclusion, these results demonstrate that sensory neurons transfer EVs-encapsulated miR-23a to activate M1 macrophages and enhance neuropathic pain following the peripheral nerve injury. The study highlighted a new therapeutic approach to alleviate chronic neuropathic pain after nerve trauma by targeting detrimental miRNA in sensory neurons.