Exosome microRNA signatures in patients with complex regional pain syndrome undergoing plasma exchange

Background Therapeutic plasma exchange (PE) or plasmapheresis is an extracorporeal procedure employed to treat immunological disorders. Exosomes, nanosized vesicles of endosomal origin, mediate intercellular communication by transferring cargo proteins and nucleic acids and regulate many pathophysio...

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Veröffentlicht in:Journal of translational medicine Jg. 17; H. 1; S. 81 - 12
Hauptverfasser: Ramanathan, Sujay, Douglas, Sabrina R., Alexander, Guillermo M., Shenoda, Botros B., Barrett, James E., Aradillas, Enrique, Sacan, Ahmet, Ajit, Seena K.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 14.03.2019
BioMed Central Ltd
Springer Nature B.V
BMC
Schlagworte:
3' Untranslated regions
3' Untranslated Regions - genetics
Adult
Apheresis
Base Sequence
Biological markers
Biomarker
Biomarkers
Biomedical and Life Sciences
Biomedicine
Care and treatment
Cell signaling
Chronic pain
Communication
Complex regional pain syndrome
Complex Regional Pain Syndromes - blood
Complex Regional Pain Syndromes - genetics
Critical Care and Anesthesia
Cytokines
Exosomes
Exosomes - genetics
Exosomes - ultrastructure
Female
Gene expression
Gene Expression Regulation
Gene regulation
Genes
Genetic regulation
Health aspects
HEK293 Cells
High performance liquid chromatography
Humans
Inflammation
Interleukin 6
Interleukin-6 - blood
Interleukin-6 - genetics
Interleukin-6 - metabolism
Interleukins
Luciferase
Male
Medical prognosis
Medical schools
Medicine/Public Health
Messenger RNA
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
miRNA
mRNA
Nucleic acids
Pain
Patients
Plasma Exchange
Plasma exchange (Therapeutics)
Plasmapheresis
Proteins
RNA
RNA, Messenger - genetics
RNA, Messenger - metabolism
Somatoform disorders
Studies
Systematic review
THP-1 Cells
Transfection
Transplants & implants
Tumor Necrosis Factor-alpha - blood
United States
Plasma exchange
miRNA
Biomarker
Inflammation
Exosomes
ISSN:1479-5876, 1479-5876
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Zusammenfassung:Background Therapeutic plasma exchange (PE) or plasmapheresis is an extracorporeal procedure employed to treat immunological disorders. Exosomes, nanosized vesicles of endosomal origin, mediate intercellular communication by transferring cargo proteins and nucleic acids and regulate many pathophysiological processes. Exosomal miRNAs are potential biomarkers due to their stability and dysregulation in diseases including complex regional pain syndrome (CRPS), a chronic pain disorder with persistent inflammation. A previous study showed that a subset of CRPS patients responded to PE. Methods As a proof-of-concept, we investigated the PE-induced exosomal miRNA changes in six CRPS patients. Plasma cytokine levels were measured by HPLC and correlated with miRNA expression. Luciferase assay following co-transfection of HEK293 cells with target 3′UTR constructs and miRNA mimics was used to evaluate miRNA mediated gene regulation of target mRNA. Transient transfection of THP-1 cells with miRNA mimics followed by estimation of target gene and protein expression was used to validate the findings. Results Comparison of miRNAs in exosomes from the serum of three responders and three poor-responders showed that 17 miRNAs differed significantly before and after therapy. Of these, poor responders had lower exosomal hsa-miR-338-5p. We show that miR-338-5p can bind to the interleukin 6 (IL-6) 3′ untranslated region and can regulate IL-6 mRNA and protein levels in vitro. PE resulted in a significant reduction of IL-6 in CRPS patients. Conclusions We propose that lower pretreatment levels of miR-338-5p in poor responders are linked to IL-6 levels and inflammation in CRPS. Our data suggests the feasibility of exploring exosomal miRNAs as a strategy in patient stratification for maximizing therapeutic outcome of PE.
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ISSN:1479-5876
1479-5876
DOI:10.1186/s12967-019-1833-3