miR-18b attenuates cerebral ischemia/reperfusion injury through regulation of ANXA3 and PI3K/Akt signaling pathway.

Abstract

Recent, research has displayed that the disorders of miR-18b are related to ischemic stroke. Here, we aimed to investigate the underlying neuroprotective mechanism of miR-18b in cerebral ischemia/reperfusion (I/R) injury. Oxygen-glucose deprivation/reperfusion (OGDR) model in vitro and middle cerebral artery occlusion (MCAO) model in vivo were established to simulate cerebral I/R injury. RT-PCR, western blotting, CCK-8, TUNEL, and TTC staining assays were applied in this study to explore the effect of miR-18b on cerebral I/R injury. Results displayed that miR-18b expression was reduced after cerebral I/R injury. Besides, miR-18b showed neuroprotective effects on cerebral I/R injury both in vitro and in vivo, These neuroprotective effects included promoting cell viability, decreasing cell apoptosis, reducing the production of inflammatory cytokines in SH-SY 5Y cells after OGDR and depressing MCAO-induced infarct size, neurological deficits and apoptotic cells in mice. Moreover, miR-18b negatively regulated ANXA3 expression, and its neuroprotection on cerebral I/R injury was overturned by ANXA3. Additionally, increasing miR-18b or decreasing ANXA3 promoted the activation of the PI3K/Akt signaling pathway in SH-SY 5Y cells after cerebral I/R injury. In conclusion, these data indicate that miR-18b protects against cerebral I/R injury by inhibiting ANXA3 and activating PI3K/Akt pathway, which provides a promising therapeutic target for ischemic stroke therapy.

• Authors: Xiao-Li Min, Mu He, Ying Shi, Ling Xie, Xiao-Jia Ma, Yi Cao
• Journal: Brain research bulletin (Brain Res Bull) Vol. 161 Pg. 55-64 (08 2020) ISSN: 1873-2747 [Electronic] United States
• PMID: 32380186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• ANXA3 protein, human
• MIRN18 microRNA, human
• MicroRNAs
• Proto-Oncogene Proteins c-akt
• Annexin A3

Topics

• Animals
• Annexin A3 (antagonists & inhibitors, biosynthesis, genetics)
• Brain Ischemia (genetics, metabolism, prevention & control)
• Cell Line, Tumor
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• MicroRNAs (biosynthesis, genetics)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Reperfusion Injury (genetics, metabolism, prevention & control)
• Signal Transduction (physiology)