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Open Access 29-07-2022 | Cerebral Ischemia | Original Article

MicroRNA-193a-5p Rescues Ischemic Cerebral Injury by Restoring N2-Like Neutrophil Subsets

Authors: Ziping Han, Lingzhi Li, Haiping Zhao, Rongliang Wang, Feng Yan, Zhen Tao, Junfen Fan, Yangmin Zheng, Fangfang Zhao, Yuyou Huang, Yue Tian, Guangwen Li, Yumin Luo

Published in: Translational Stroke Research | Issue 4/2023

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Abstract

Circulating neutrophils are activated shortly after stroke and in turn affect the fate of ischemic brain tissue, and microRNAs (miRNA) participate in regulating neuroinflammation. We probed the role of neutrophilic miRNA in ischemic stroke. miR-193a-5p was decreased in circulating neutrophils of acute ischemic stroke (AIS) patients and healthy controls. In another set of AIS patients treated with recombinant tissue plasminogen activator, higher neutrophilic miR-193a-5p levels were associated with favorable outcomes at 3 months and non-symptomatic intracerebral hemorrhage. An experimental stroke model and human neutrophil-like HL-60 cells were further transfected with agomiR-193a-5p/antagomiR-193a-5p or ubiquitin-conjugating enzyme V2 (UBE2V2)-siRNA prior to model induction for in vivo and in vitro studies. Results of 2,3,5-triphenyl tetrazolium chloride staining and neurological function evaluations at post-experimental stroke showed that intravenous agomiR-193a-5p transfusion protected against ischemic cerebral injury in the acute stage and promoted neurological recovery in the subacute stage. This protective role was suggested to correlate with neutrophil N2 transformation based on the N2-like neutrophil proportions in the bone marrow, peripheral blood, and spleen of the experimental stroke model and the measurement of neutrophil phenotype-associated molecule levels. Mechanistically, analyses indicated that UBE2V2 might be a target of miR-193a-5p. Cerebral injury and neuroinflammation aggravated by miR-193a-5p inhibition were reversed by UBE2V2 silencing. In conclusion, miR-193a-5p protects against cerebral ischemic injury by restoring neutrophil N2 phenotype-associated neuroinflammation suppression, likely, in part, via UBE2V2 induction.
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Metadata
Title
MicroRNA-193a-5p Rescues Ischemic Cerebral Injury by Restoring N2-Like Neutrophil Subsets
Authors
Ziping Han
Lingzhi Li
Haiping Zhao
Rongliang Wang
Feng Yan
Zhen Tao
Junfen Fan
Yangmin Zheng
Fangfang Zhao
Yuyou Huang
Yue Tian
Guangwen Li
Yumin Luo
Publication date
29-07-2022
Publisher
Springer US
Published in
Translational Stroke Research / Issue 4/2023
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-022-01071-y