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MicroRNA-532-5p protects against cerebral ischemia-reperfusion injury by directly targeting CXCL1
- Source :
- Aging (Albany NY)
- Publication Year :
- 2021
- Publisher :
- Impact Journals, 2021.
-
Abstract
- We investigated the function of microRNA (miR)-532-5p in cerebral ischemia-reperfusion injury (CI/RI) and the underlying mechanisms using oxygen-glucose deprivation and reperfusion (OGD/R)-treated SH-SY5Y cells and middle cerebral artery occlusion (MCAO) model rats. MiR-532-5p levels were significantly downregulated in OGD/R-treated SH-SY5Y cells and the brain tissues of MCAO model rats. MiR-532-5p overexpression significantly reduced apoptosis, reactive oxygen species (ROS), and inflammation in the OGD/R-induced SH-SY5Y cells. Bioinformatics analysis using the targetscan and miRDB databases as well as dual luciferase reporter assays confirmed that miR-532-5p directly binds to the 3'UTR of C-X-C Motif Ligand 1 (CXCL1). Methylation-specific PCR (MSP) analysis showed that miR-532-5p expression was reduced in OGD/R-treated SH-SY5Y cells because of miR-532-5p promoter hypermethylation. Moreover, 5-azacytidine, a methylation inhibitor, restored miR-532-5p expression in OGD/R-treated SH-SY5Y cells. Brain tissues of MCAO model rats showed significantly increased cerebral infarction areas, cerebral water, neuronal apoptosis, and activated CXCL1/CXCR2/NF-κB signaling, but these effects were alleviated by intraventricular injection of miR-532-5p agomir. These findings demonstrate that miR-532-5p overexpression significantly reduces in vitro and in vivo CI/RI by targeting CXCL1. Thus, miR-532-5p is a potential therapeutic target for patients with CI/RI.
- Subjects :
- Aging
Chemokine CXCL1
Ischemia
Down-Regulation
Inflammation
Apoptosis
Pharmacology
NF-κB
In vivo
Cell Line, Tumor
medicine
Animals
Humans
Rats, Wistar
Injections, Intraventricular
chemistry.chemical_classification
Neurons
Reactive oxygen species
CXCR2
Cerebral infarction
Brain
Computational Biology
Infarction, Middle Cerebral Artery
Cell Biology
medicine.disease
CXCL1
Rats
MicroRNAs
chemistry
miR-532-5p
Reperfusion Injury
medicine.symptom
Reperfusion injury
Research Paper
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19454589
- Volume :
- 13
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Aging (Albany NY)
- Accession number :
- edsair.doi.dedup.....db3208157640631f9eb04702e70f6b28