Research Paper Advance Articles

miR-183-5p alleviates early injury after intracerebral hemorrhage by inhibiting heme oxygenase-1 expression

Yu Wang1, , Yuejia Song2, , Yuxin Pang1, , Zihan Yu1, , Wei Hua1, , Yunhe Gu1, , Jiping Qi1, , He Wu1, ,

  • 1 Department of Pathology, First Clinical Hospital, Harbin Medical University, Harbin 150001, China
  • 2 Department of Endocrinology, First Clinical Hospital, Harbin Medical University, Harbin 150001, China
* Equal contribution

Received: January 11, 2020       Accepted: May 18, 2020       Published: June 29, 2020      

https://doi.org/10.18632/aging.103343
How to Cite

Copyright © 2020 Wang 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.

Abstract

Differences in microRNA (miRNA) expression after intracerebral hemorrhage (ICH) have been reported in human and animal models, and miRNAs are being investigated as a new treatment for inflammation and oxidative stress after ICH. In this study, we found that microRNA-183-5p expression was decreased in the mouse brain after ICH. To investigate the effect of miRNA-183-5p on injury and repair of brain tissue after ICH, saline, miRNA-183-5p agomir, or miRNA-183-5p antagomir were injected into the lateral ventricles of 8-week-old mice with collagenase-induced ICH. Three days after ICH, mice treated with exogenous miRNA-183-5p showed less brain edema, neurobehavioral defects, inflammation, oxidative stress, and ferrous deposition than control mice. In addition, by alternately treating mice with a heme oxygenase-1 (HO-1) inducer, a HO-1 inhibitor, a nuclear factor erythroid 2-related factor (Nrf2) activator, and Nrf2 knockout, we demonstrated an indirect, HO-1-dependent regulatory relationship between miRNA-183-5p and Nrf2. Our results indicate that miRNA-183-5p and HO-1 are promising therapeutic targets for controlling inflammation and oxidative damage after hemorrhagic stroke.

Abbreviations

miRNA: microRNA; ICH: intracerebral hemorrhage; miRNA-183-5p: microRNA-183-5p; HO-1: heme oxygenase-1; Nrf2: nuclear factor erythroid 2-related factor; BBB: blood-brain barrier; miRNA-Seq: miRNA sequencing; ELISA: enzyme-linked immunosorbent assay; ROS: reactive oxygen species; EB: Evans blue; agomir-183-5p: miR-183-5p agomir; antagomir-183-5p: miR-183-5p antagomir; ZnPP: zinc protoporphyrin IX; Nrf2-/-: Nrf2 knockout; CoPP: cobalt protoporphyrin IX; WT: wild type; tBHQ: tert-butylhydroquinone; IP: intraperitoneal injection; DMSO: dimethyl sulfoxide; Iba-1: ionized calcium binding adapter molecule 1; MPO: myeloperoxidase; 3’-UTR: 3’-untranslated region; MUT: mutant; HEK293: human embryonic kidney 293; miR-183-5p: MM miR-183-5p mimic; NC: nontarget control; CCK-8: Cell Counting Kit-8; Ipsi-Stri: ipsilateral striatum; Con-Stri: contralateral striatum; Cerebel: cerebellum; AREs: antioxidant response elements; Fe2+: ferrous iron; CO: ca:bon monoxide.