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MiR-377 Regulates Inflammation and Angiogenesis in Rats After Cerebral Ischemic Injury
Yiling Fan1, Shenghao Ding1, Yameng Sun1
1Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Abstract:
Ischemic stroke is the leading cause of disabilities worldwide. MicroRNA-377 (miR-377) plays important roles in ischemic injury. The present study focused on the mechanisms of miR-377 in protecting ischemic brain injury in rats. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in rats. Primary rat microglial cells and brain microvascular endothelial cells (BMECs) were exposed to oxygen-glucose deprivation (OGD). The concentrations of cytokines (TNF-α, IL-1β, IL-6, IFN-γ, TGF-β, MMP2, COX2, and iNOS) in the culture medium were measured by specific ELISA. Tube formation assay was for the in vitro study of angiogenesis. Luciferase reporter assay was performed to confirm whether VEGF and EGR2 were direct targets of miR-377. The MCAO rats were intracerebroventricular (ICV) injection of miR-377 inhibitor to assess its protective effects in vivo. MiR-377 levels were decreased in the rat brain tissues at 1, 3, and 7 d after MCAO. Both microglia cells and BMECs under OGD showed markedly lower expression levels of miR-377 while higher expression levels of EGR2 and VEGF compared to those under normoxia conditions. Knockdown of miR-377 inhibited microglial activation and the release of pro-inflammatory cytokines after OGD. Suppression of miR-377 promoted the capillary-like tube formation and cell proliferation and migration of BMECs. The anti-inflammation effect of EGR2 and the angiogenesis effect of VEGF were regulated by miR-377 after OGD. Inhibition of miR-377 decreased cerebral infarct volume and suppressed cerebral inflammation but promoted angiogenesis in MCAO rats. Knockdown of miR-377 lessened the ischemic brain injury through promoting angiogenesis and suppressing cerebral inflammation. J. Cell. Biochem. 119: 327-337, 2018. © 2017 Wiley Periodicals, Inc.
Insights
MicroRNA-377 (miR-377) protects against ischemic brain injury by reducing inflammation and promoting blood vessel formation. Lowering miR-377 worsened stroke outcomes in rats.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Ischemic stroke is a major cause of global disability.
- MicroRNA-377 (miR-377) is implicated in the response to ischemic injury.
- Understanding miR-377's protective mechanisms is crucial for developing stroke therapies.
Purpose of the Study:
- To investigate the protective mechanisms of miR-377 in rat models of ischemic brain injury.
- To elucidate the role of miR-377 in regulating microglial activation, inflammation, and angiogenesis.
Main Methods:
- Middle cerebral artery occlusion (MCAO) model in rats and oxygen-glucose deprivation (OGD) in vitro.
- Measurement of cytokine levels, angiogenesis, and gene expression (EGR2, VEGF).
- In vivo assessment using intracerebroventricular injection of miR-377 inhibitor.
Main Results:
- miR-377 levels decreased post-MCAO and during OGD.
- miR-377 knockdown increased pro-inflammatory cytokines and inhibited angiogenesis.
- miR-377 targeted EGR2 and VEGF, modulating inflammation and angiogenesis.
- Inhibition of miR-377 worsened stroke outcomes in rats.
Conclusions:
- miR-377 exerts protective effects against ischemic brain injury.
- miR-377 suppresses inflammation and promotes angiogenesis via EGR2 and VEGF.
- Restoring miR-377 levels may be a therapeutic strategy for ischemic stroke.
