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. [Figure not available: see fulltext.]
|Number of pages||10|
|Journal||Journal of NeuroImmune Pharmacology|
|State||Published - Sep 1 2020|
Bibliographical noteFunding Information:
This work was supported by grants DA042704, DA046831, MH112848, and DA043138 from the National Institutes of Health (NIH). The support of the Nebraska Center for Substance Abuse Research is acknowledged. The project described was also supported by the NIH, National Institute of Mental Health, 2P30MH062261. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We would like to thank Dr. Shilpa Buch for highly useful comments and suggestions that greatly improved the manuscript. Also, we are grateful to Shannon Callen for comments.
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
- Extracellular vesicle
- Intranasal delivery
- Microglial proliferation
ASJC Scopus subject areas
- Neuroscience (miscellaneous)
- Immunology and Allergy