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Updated: Aug 8, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Exosomal Mir-3613-3p derived from oxygen-glucose deprivation-treated brain microvascular endothelial cell promotes
Mengqi Zhang1,2, Qian Wu3, Mimi Tang4,5
1Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China. zhangmengqi8912@163.com.
Background:
Brain microvascular endothelial cell (BMEC) injury can affect neuronal survival by modulating immune responses through the microenvironment. Exosomes are important vehicles of transport between cells. However, the regulation of the subtypes of microglia by BMECs through the exosome transport of microRNAs (miRNAs) has not been established.
Methods:
In this study, exosomes from normal and oxygen-glucose deprivation (OGD)-cultured BMECs were collected, and differentially expressed miRNAs were analyzed. BMEC proliferation, migration, and tube formation were analyzed using MTS, transwell, and tube formation assays. M1 and M2 microglia and apoptosis were analyzed using flow cytometry. miRNA expression was analyzed using real-time polymerase chain reaction (RT-qPCR), and IL-1β, iNOS, IL-6, IL-10, and RC3H1 protein concentrations were analyzed using western blotting.
Results:
We found that miR-3613-3p was enriched in BMEC exosome by miRNA GeneChip assay and RT-qPCR analysis. miR-3613-3p knockdown enhanced cell survival, migration, and angiogenesis in the OGD-treated BMECs. In addition, BMECs secrete miR-3613-3p to transfer into microglia via exosomes, and miR-3613-3p binds to the RC3H1 3' untranslated region (UTR) to reduce RC3H1 protein levels in microglia. Exosomal miR-3613-3p promotes microglial M1 polarization by inhibiting RC3H1 protein levels. BMEC exosomal miR-3613-3p reduces neuronal survival by regulating microglial M1 polarization.
Conclusions:
miR-3613-3p knockdown enhances BMEC functions under OGD conditions. Interfering with miR-3613-3p expression in BMSCs reduced the enrichment of miR-3613-3p in exosomes and enhanced M2 polarization of microglia, which contributed to reduced neuronal apoptosis.
Insights
Brain microvascular endothelial cells release miR-3613-3p via exosomes, promoting M1 microglia polarization and reducing neuronal survival. Knockdown of miR-3613-3p improves brain endothelial cell function and reduces neuronal apoptosis.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Brain microvascular endothelial cell (BMEC) injury impacts neuronal survival via immune modulation. Exosomes mediate intercellular communication, but their role in BMEC regulation of microglia subtypes via microRNAs (miRNAs) is unclear.
- Investigating the role of exosomal miRNAs in the communication between brain microvascular endothelial cells and microglia is crucial for understanding neuroinflammatory processes.
Discussion:
- Exosomes secreted by oxygen-glucose deprivation (OGD)-treated BMECs contain enriched miR-3613-3p.
- miR-3613-3p targets the RC3H1 3' untranslated region (UTR) in microglia, inhibiting RC3H1 protein expression.
- Exosomal miR-3613-3p promotes M1 microglia polarization, contributing to reduced neuronal survival.
Key Insights:
- miR-3613-3p is a key miRNA transferred from BMECs to microglia via exosomes.
- Knockdown of miR-3613-3p in BMECs enhances their survival, migration, and angiogenesis under OGD conditions.
- Interfering with exosomal miR-3613-3p promotes M2 microglia polarization and reduces neuronal apoptosis.
Outlook:
- Targeting exosomal miR-3613-3p may offer a therapeutic strategy for neurodegenerative diseases associated with neuroinflammation.
- Further research is needed to elucidate the precise mechanisms of miR-3613-3p in regulating microglia polarization and neuronal function.
- Exploring the potential of BMEC-derived exosomes as delivery vehicles for therapeutic miRNAs in neurological disorders.
