Cargando…

Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma

Following peripheral axon injury, dysregulation of non-coding microRNAs (miRs) occurs in dorsal root ganglia (DRG) sensory neurons. Here we show that DRG neuron cell bodies release extracellular vesicles, including exosomes containing miRs, upon activity. We demonstrate that miR-21-5p is released in...

Descripción completa

Detalles Bibliográficos
Autores principales: Simeoli, Raffaele, Montague, Karli, Jones, Hefin R., Castaldi, Laura, Chambers, David, Kelleher, Jayne H., Vacca, Valentina, Pitcher, Thomas, Grist, John, Al-Ahdal, Hadil, Wong, Liang-Fong, Perretti, Mauro, Lai, Johnathan, Mouritzen, Peter, Heppenstall, Paul, Malcangio, Marzia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701122/
https://www.ncbi.nlm.nih.gov/pubmed/29176651
http://dx.doi.org/10.1038/s41467-017-01841-5
_version_ 1783281271570432000
author Simeoli, Raffaele
Montague, Karli
Jones, Hefin R.
Castaldi, Laura
Chambers, David
Kelleher, Jayne H.
Vacca, Valentina
Pitcher, Thomas
Grist, John
Al-Ahdal, Hadil
Wong, Liang-Fong
Perretti, Mauro
Lai, Johnathan
Mouritzen, Peter
Heppenstall, Paul
Malcangio, Marzia
author_facet Simeoli, Raffaele
Montague, Karli
Jones, Hefin R.
Castaldi, Laura
Chambers, David
Kelleher, Jayne H.
Vacca, Valentina
Pitcher, Thomas
Grist, John
Al-Ahdal, Hadil
Wong, Liang-Fong
Perretti, Mauro
Lai, Johnathan
Mouritzen, Peter
Heppenstall, Paul
Malcangio, Marzia
author_sort Simeoli, Raffaele
collection PubMed
description Following peripheral axon injury, dysregulation of non-coding microRNAs (miRs) occurs in dorsal root ganglia (DRG) sensory neurons. Here we show that DRG neuron cell bodies release extracellular vesicles, including exosomes containing miRs, upon activity. We demonstrate that miR-21-5p is released in the exosomal fraction of cultured DRG following capsaicin activation of TRPV1 receptors. Pure sensory neuron-derived exosomes released by capsaicin are readily phagocytosed by macrophages in which an increase in miR-21-5p expression promotes a pro-inflammatory phenotype. After nerve injury in mice, miR-21-5p is upregulated in DRG neurons and both intrathecal delivery of a miR-21-5p antagomir and conditional deletion of miR-21 in sensory neurons reduce neuropathic hypersensitivity as well as the extent of inflammatory macrophage recruitment in the DRG. We suggest that upregulation and release of miR-21 contribute to sensory neuron–macrophage communication after damage to the peripheral nerve.
format Online
Article
Text
id pubmed-5701122
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-57011222017-11-27 Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma Simeoli, Raffaele Montague, Karli Jones, Hefin R. Castaldi, Laura Chambers, David Kelleher, Jayne H. Vacca, Valentina Pitcher, Thomas Grist, John Al-Ahdal, Hadil Wong, Liang-Fong Perretti, Mauro Lai, Johnathan Mouritzen, Peter Heppenstall, Paul Malcangio, Marzia Nat Commun Article Following peripheral axon injury, dysregulation of non-coding microRNAs (miRs) occurs in dorsal root ganglia (DRG) sensory neurons. Here we show that DRG neuron cell bodies release extracellular vesicles, including exosomes containing miRs, upon activity. We demonstrate that miR-21-5p is released in the exosomal fraction of cultured DRG following capsaicin activation of TRPV1 receptors. Pure sensory neuron-derived exosomes released by capsaicin are readily phagocytosed by macrophages in which an increase in miR-21-5p expression promotes a pro-inflammatory phenotype. After nerve injury in mice, miR-21-5p is upregulated in DRG neurons and both intrathecal delivery of a miR-21-5p antagomir and conditional deletion of miR-21 in sensory neurons reduce neuropathic hypersensitivity as well as the extent of inflammatory macrophage recruitment in the DRG. We suggest that upregulation and release of miR-21 contribute to sensory neuron–macrophage communication after damage to the peripheral nerve. Nature Publishing Group UK 2017-11-24 /pmc/articles/PMC5701122/ /pubmed/29176651 http://dx.doi.org/10.1038/s41467-017-01841-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Simeoli, Raffaele
Montague, Karli
Jones, Hefin R.
Castaldi, Laura
Chambers, David
Kelleher, Jayne H.
Vacca, Valentina
Pitcher, Thomas
Grist, John
Al-Ahdal, Hadil
Wong, Liang-Fong
Perretti, Mauro
Lai, Johnathan
Mouritzen, Peter
Heppenstall, Paul
Malcangio, Marzia
Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma
title Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma
title_full Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma
title_fullStr Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma
title_full_unstemmed Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma
title_short Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma
title_sort exosomal cargo including microrna regulates sensory neuron to macrophage communication after nerve trauma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701122/
https://www.ncbi.nlm.nih.gov/pubmed/29176651
http://dx.doi.org/10.1038/s41467-017-01841-5
work_keys_str_mv AT simeoliraffaele exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT montaguekarli exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT joneshefinr exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT castaldilaura exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT chambersdavid exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT kelleherjayneh exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT vaccavalentina exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT pitcherthomas exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT gristjohn exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT alahdalhadil exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT wongliangfong exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT perrettimauro exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT laijohnathan exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT mouritzenpeter exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT heppenstallpaul exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma
AT malcangiomarzia exosomalcargoincludingmicrornaregulatessensoryneurontomacrophagecommunicationafternervetrauma