Morphine-mediated release of miR-138 in astrocyte-derived extracellular vesicles promotes microglial activation.


Journal

Journal of extracellular vesicles
ISSN: 2001-3078
Titre abrégé: J Extracell Vesicles
Pays: United States
ID NLM: 101610479

Informations de publication

Date de publication:
10 2020
Historique:
received: 07 05 2020
revised: 20 09 2020
accepted: 15 10 2020
entrez: 11 12 2020
pubmed: 12 12 2020
medline: 12 12 2020
Statut: ppublish

Résumé

Opioids, such as morphine, are the mainstay for the management of postsurgical pain. Over the last decade there has been a dramatic increase in deaths related to opioid overdose. While opioid abuse has been shown to result in increased neuroinflammation, mechanism(s) underlying this process, remain less understood. In recent years, microRNAs have emerged as key mediators of gene expression regulating both paracrine signaling and cellular crosstalk. MiRNAs constitute the extracellular vesicle (EV) cargo and can shuttle from the donor to the recipient cells. Exposure of human primary astrocytes to morphine resulted in induction and release of miR-138 in the EVs isolated from conditioned media of cultured astrocytes. Released EVs were, in turn, taken up by the microglia, leading to activation of these latter cells. Interestingly, activation of microglia involved binding of the GUUGUGU motif of miR138 to the endosomal toll like receptor (TLR)7, leading, in turn, to cellular activation. These findings were further corroborated in vivo in wildtype mice wherein morphine administration resulted in increased microglial activation in the thalamus. In TLR7

Identifiants

pubmed: 33304479
doi: 10.1002/jev2.12027
pii: JEV212027
pmc: PMC7710131
doi:

Substances chimiques

MIRN138 microRNA, mouse 0
Membrane Glycoproteins 0
MicroRNAs 0
Tlr7 protein, mouse 0
Toll-Like Receptor 7 0
Morphine 76I7G6D29C

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Pagination

e12027

Subventions

Organisme : NIMH NIH HHS
ID : P30 MH062261
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA040397
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA041751
Pays : United States

Informations de copyright

© 2020 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

Déclaration de conflit d'intérêts

The authors declare no competing financial interests in relation to the work described.

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Auteurs

Ke Liao (K)

Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha Nebraska USA.

Fang Niu (F)

Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha Nebraska USA.

Guoku Hu (G)

Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha Nebraska USA.

Lu Yang (L)

Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha Nebraska USA.

Blake Dallon (B)

Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha Nebraska USA.

Delaney Villarreal (D)

Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha Nebraska USA.

Shilpa Buch (S)

Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha Nebraska USA.

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Classifications MeSH