PMID- 31489147
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2001-3078 (Print)
IS  - 2001-3078 (Electronic)
IS  - 2001-3078 (Linking)
VI  - 8
IP  - 1
DP  - 2019
TI  - Inflammation potentiates miR-939 expression and packaging into small 
      extracellular vesicles.
PG  - 1650595
LID - 10.1080/20013078.2019.1650595 [doi]
LID - 1650595
AB  - Extracellular RNA in circulation mediates intercellular communication in normal 
      and pathological processes. One mode of circulating miRNA transport in bodily 
      fluids is within 30-150 nm small extracellular vesicles (sEVs) or exosomes. 
      Uptake of sEVs can regulate gene expression in recipient cells enabling 
      circulating miRNAs to exert paracrine and systemic effects. Complex regional pain 
      syndrome (CRPS) is a debilitating pain disorder characterized by chronic 
      inflammation. Our previous investigations identified a significant decrease of 
      hsa-miR-939 in whole blood from CRPS patients compared to control; we also 
      observed that overexpression of miR-939 can negatively regulate several 
      proinflammatory genes in vitro. Though downregulated in whole blood, miR-939 was 
      significantly upregulated in sEVs isolated from patient serum. Here we 
      investigated miR-939 packaging into sEVs in vitro under inflammation induced by 
      monocyte chemoattractant protein-1 (MCP-1), a chemokine that is upregulated in 
      CRPS patients. Stimulation of THP-1 monocytes by MCP-1 led to elevated levels of 
      miR-939 in sEVs, which was abrogated using inhibitors of exosome secretion. 
      miRNAs loaded into exosomes largely contain short miRNA sequence motifs called 
      EXOmotifs. Mutation analysis of miR-939 showed that EXOmotif is one of the 
      possible cellular mechanisms responsible for packaging miR-939 into sEVs. We 
      confirmed gene expression changes in recipient cells following the uptake of sEVs 
      enriched in miR-939 using RNA sequencing. Additionally, our data from primary 
      immune cell-derived sEVs of CRPS patients and controls demonstrate that while the 
      relative expression of miR-939 is higher in sEVs derived from B cells, T cells 
      and NK cells relative to monocyte-derived sEVs in controls, only the B 
      cell-derived sEVs showed a significantly higher level of miR-939 in CRPS 
      patients. Differential miRNA sorting into exosomes and its functional impact on 
      recipient cells may contribute to the underlying pathophysiology of CRPS.
FAU - Ramanathan, Sujay
AU  - Ramanathan S
AD  - Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, 
      PA, USA.
FAU - Shenoda, Botros B
AU  - Shenoda BB
AD  - Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, 
      PA, USA.
FAU - Lin, Zhucheng
AU  - Lin Z
AD  - Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, 
      PA, USA.
FAU - Alexander, Guillermo M
AU  - Alexander GM
AD  - Neurology, Drexel University College of Medicine, Philadelphia, PA, USA.
FAU - Huppert, Arthur
AU  - Huppert A
AD  - Rheumatology, Hahnemann University Hospital, Philadelphia, PA, USA.
FAU - Sacan, Ahmet
AU  - Sacan A
AD  - School of Biomedical Engineering, Science & Health Systems, Drexel University, 
      Philadelphia, PA, USA.
FAU - Ajit, Seena K
AU  - Ajit SK
AUID- ORCID: 0000-0002-0822-7037
AD  - Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, 
      PA, USA.
LA  - eng
GR  - R01 NS102836/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20190806
PL  - United States
TA  - J Extracell Vesicles
JT  - Journal of extracellular vesicles
JID - 101610479
PMC - PMC6713176
OTO - NOTNLM
OT  - CRPS
OT  - EXOmotif
OT  - Extracellular vesicles
OT  - MCP-1
OT  - exosomes
OT  - inflammation
OT  - miR-939
OT  - miRNA packaging
EDAT- 2019/09/07 06:00
MHDA- 2019/09/07 06:01
PMCR- 2019/08/06
CRDT- 2019/09/07 06:00
PHST- 2019/03/23 00:00 [received]
PHST- 2019/07/23 00:00 [revised]
PHST- 2019/07/26 00:00 [accepted]
PHST- 2019/09/07 06:00 [entrez]
PHST- 2019/09/07 06:00 [pubmed]
PHST- 2019/09/07 06:01 [medline]
PHST- 2019/08/06 00:00 [pmc-release]
AID - 1650595 [pii]
AID - 10.1080/20013078.2019.1650595 [doi]
PST - epublish
SO  - J Extracell Vesicles. 2019 Aug 6;8(1):1650595. doi: 
      10.1080/20013078.2019.1650595. eCollection 2019.