Cellular & Molecular Biology Letters (Mar 2023)

Exosomal Mir-3613-3p derived from oxygen–glucose deprivation-treated brain microvascular endothelial cell promotes microglial M1 polarization

  • Mengqi Zhang,
  • Qian Wu,
  • Mimi Tang,
  • Zhuohui Chen,
  • Haiyue Wu

DOI
https://doi.org/10.1186/s11658-023-00432-1
Journal volume & issue
Vol. 28, no. 1
pp. 1 – 14

Abstract

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Abstract 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.

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