Abstract
Background: Ischemic stroke is the leading cause of disability and death globally. Micro-RNAs
(miRNAs) have been reported to play important roles in the development and pathogenesis
of the nervous system. However, the exact function and mechanism of miRNAs have not
been fully elucidated about brain damage caused by cerebral ischemia/reperfusion (I/R).
Methods: In this study, we explored the neuroprotective effects of miR-219a-5p on brain using
an in vitro ischemia model (mouse neuroblastoma N2a cells treated with oxyglucose
deprivation and reperfusion), and in vivo cerebral I/R model in mice. Western blot
assay and Reverse Transcription-Polymerase Chain Reaction were used to check the expression
of molecules involved. Flow cytometry and cholecystokinin were used to examine cell
apoptosis, respectively. Results: Our research shows that miR-219a-5p gradually decreases in cerebral I/R models in
vivo and in vitro. In vitro I/R, we find that miR-219a-5p mimics provided evidently
protection for cerebral I/R damage, as shown by increased cell viability and decreased
the release of LDH and cell apoptosis. Mechanically, our findings indicate that miR-219a-5p
binds to cAMP specific 3′, 5′-cyclic phosphodiesterase 4D (PDE4D) mRNA in the 3’-UTR
region, which subsequently leads to a decrease in Pde4d expression in I/R N2a cells.
Conclusions: Our results provide new ideas for the study of the mechanism of cerebral ischemia/reperfusion
injury, and lay the foundation for further research on the treatment of brain I/R
injury. Upregulation of miR-219a-5p decreases cerebral ischemia/reperfusion injury
by targeting Pde4d in vitro.
Key Words
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Article info
Publication history
Published online: April 02, 2020
Accepted:
March 2,
2020
Received in revised form:
January 23,
2020
Received:
January 1,
2020
Footnotes
Funding: This study was supported by the 2017 PhD Start-up Fund of Natural Science Foundation of Guangdong Province of China (2017A030310404), China Postdoctoral Science Foundation (2019M652826), National Natural Science Foundation of China (No.31800727), and Guangdong university of technology students innovation and entrepreneurship training program project (xj202011845191).
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104801
Copyright
© 2020 Elsevier Inc. All rights reserved.
