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Updated: Sep 5, 2025
A Simple Alternative to Stereotactic Injection for Brain Specific Knockdown of miRNA
Published on: December 26, 2015
miR-29c-5p knockdown reduces inflammation and blood-brain barrier disruption by upregulating LRP6
Qijun Dai1, Jian Sun2, Tianyi Dai3
1Department of Neurology, Haian Hospital of Traditional Chinese Medicine, Haian, 226600, China.
Abstract:
Blood-brain barrier participates in the pathological process of ischemic stroke. MicroRNA-29c-5p was highly expressed in clinical samples from patients with ischemic stroke. In this study, oxygen-glucose deprivation (OGD) treatment of astrocytes enhanced the permeability of brain microvascular endothelial cells (BMECs), and the miR-29c-5p expression was elevated in clinical samples from patients with ischemic stroke. For the function of miR-29c-5p in ischemic stroke, the miR-29c-5p knockdown decreased the permeability and the tight junction protein (TJP) destruction of BMECs and ameliorated the inflammation induced by OGD-treated astrocytes. Mechanistically, miR-29c-5p interacted with lipoprotein receptor-related protein 6 (LRP6) and negatively regulated the LRP6 expression in astrocytes. Moreover, the rescue assays indicated that the interference with miR-29c-5p ameliorated the TJP destruction of BMECs and inflammation caused by OGD-treated astrocytes by increasing the LRP6 expression. Together, miR-29c-5p knockdown decreased the high permeability and the TJP destruction of BMECs and ameliorated the inflammation induced by OGD-treated astrocytes by elevating LRP6 expression.
Insights
Reducing microRNA-29c-5p levels in ischemic stroke may protect the blood-brain barrier. This study shows that lowering miR-29c-5p lessens brain endothelial cell damage and inflammation by increasing LRP6 expression.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- The blood-brain barrier (BBB) is crucial in ischemic stroke pathology.
- MicroRNA-29c-5p (miR-29c-5p) is upregulated in ischemic stroke patients.
- Astrocytic damage from oxygen-glucose deprivation (OGD) increases BBB permeability.
Purpose of the Study:
- To investigate the role of miR-29c-5p in ischemic stroke-induced BBB dysfunction.
- To elucidate the underlying molecular mechanisms involving lipoprotein receptor-related protein 6 (LRP6).
Main Methods:
- Utilized oxygen-glucose deprivation (OGD) models with astrocytes and brain microvascular endothelial cells (BMECs).
- Measured miR-29c-5p expression and its impact on BMEC permeability and tight junction proteins (TJPs).
- Investigated the interaction between miR-29c-5p and LRP6 using knockdown and rescue assays.
Main Results:
- OGD-induced astrocytes increased BMEC permeability and TJP destruction, correlating with elevated miR-29c-5p.
- Knockdown of miR-29c-5p reduced BMEC permeability, TJP damage, and inflammation.
- miR-29c-5p directly targets and downregulates LRP6 expression in astrocytes.
- Restoring LRP6 expression reversed the protective effects of miR-29c-5p inhibition.
Conclusions:
- miR-29c-5p exacerbates ischemic stroke by increasing BBB permeability and inflammation.
- Inhibition of miR-29c-5p mitigates BBB damage and inflammation via LRP6 upregulation.
- Targeting miR-29c-5p represents a potential therapeutic strategy for ischemic stroke.
