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Cited by 54Extracellular vesicles in diseaseRNA Interference and Gene DeliveryNeuroinflammation and Neurodegeneration Mechanisms

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Intranasal delivery of lincRNA-Cox2 siRNA loaded extracellular vesicles decreases lipopolysaccharide-induced microglial proliferation in mice.

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Liao, Ke, Niu, Fang, Dagur, Raghubendra Singh, He, Mengfan, Tian, Changhai, Hu, Guoku·2020·Journal of Neuroimmune Pharmacology
DOI 10.1007/s11481-019-09864-zPMC PMC6980430
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Abstract

Long non-coding RNAs (lncRNAs), including long intergenic non-coding RNAs (lincRNAs), play an important regulatory role in controlling various biological processes. Both in vitro and in vivo studies have demonstrated that lincRNA-Cox2 plays a global regulatory role in regulating the expression of immune genes. Extracellular vesicles (EVs) are cell-derived nanosized membrane vesicles that have gained increasing attention in recent years due to their ability to efficiently deliver therapeutics to specific target organs or cell types. In this study, we found that lincRNA-Cox2 controls the expression of a set of cell cycle genes in lipopolysaccharide (LPS)-stimulated microglial cells. Our in vitro study suggested that knocking down lincRNA-Cox2 reversed LPS-induced microglial proliferation. In addition, our in vivo study demonstrated that intranasally delivered lincRNA-Cox2-siRNA loaded EVs could reach the brain resulting in a significant decrease in the expression of lincRNA-Cox2 in the microglia. Importantly, lincRNA-Cox2-siRNA loaded EVs also decreased LPS-induced microglial proliferation in mice. These findings indicate that intranasal delivery of EV-loaded small RNA could be developed as therapeutics for treatment of a multitude of CNS disorders.

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Metadata

Authors
Liao, K., Niu, F., Dagur, R. S., He, M., Tian, C., & Hu, G.
Affiliations
  • Nebraska Medical Center (US)
  • Tongji University (CN)
  • University of Nebraska Medical Center (US)
Corresponding author
Hu, Guoku
ORCID
Venue
Journal of Neuroimmune Pharmacology
Publisher
Springer Science and Business Media LLC
Published
2019-07-20
Volume
15
Issue
3
Pages
390-399
ISSN
  • 1557-1890 (ISSN-L)
  • 1557-1904
DOI
10.1007/s11481-019-09864-z
PMC
PMC6980430
OpenAlex
W2964083827
Cited by
54
References
3
Citations by year
2026: 5 · 2025: 8 · 2024: 9 · 2023: 7 · 2022: 5 · 2021: 9 · 2020: 9 · 2019: 2
FWCI
1.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroimmune Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (DA042704, DA046831, MH112848, and DA043138)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
long intergenic non-coding RNA, extracellular vesicles, siRNA delivery, intranasal drug delivery, microglial proliferation, lipopolysaccharide, cell cycle genes, neuroinflammation, CNS therapeutics, gene silencing
MeSH terms
Extracellular Vesicles, Administration, Intranasal, Animals, Cell Line, Lipopolysaccharides, Mice, Inbred C57BL, Drug Delivery Systems, Microglia, Genes, cdc, RNA, Small Interfering, Cell Proliferation, Mice, Cyclooxygenase 2, Nanoparticles, RNA, Long Noncoding

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