Exosome microRNA signatures in patients with complex regional pain syndrome undergoing plasma exchange
Abstract 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 pa...
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-019-1833-3 |
| _version_ | 1818919971164520448 |
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| author | Sujay Ramanathan Sabrina R. Douglas Guillermo M. Alexander Botros B. Shenoda James E. Barrett Enrique Aradillas Ahmet Sacan Seena K. Ajit |
| author_facet | Sujay Ramanathan Sabrina R. Douglas Guillermo M. Alexander Botros B. Shenoda James E. Barrett Enrique Aradillas Ahmet Sacan Seena K. Ajit |
| author_sort | Sujay Ramanathan |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-20T01:14:20Z |
| format | Article |
| id | doaj.art-fb344a0242974c5190bca45c06a856f0 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-20T01:14:20Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-fb344a0242974c5190bca45c06a856f02022-12-21T19:58:37ZengBMCJournal of Translational Medicine1479-58762019-03-0117111210.1186/s12967-019-1833-3Exosome microRNA signatures in patients with complex regional pain syndrome undergoing plasma exchangeSujay Ramanathan0Sabrina R. Douglas1Guillermo M. Alexander2Botros B. Shenoda3James E. Barrett4Enrique Aradillas5Ahmet Sacan6Seena K. Ajit7Pharmacology & Physiology, Drexel University College of MedicinePharmacology & Physiology, Drexel University College of MedicineNeurology, Drexel University College of MedicinePharmacology & Physiology, Drexel University College of MedicinePharmacology & Physiology, Drexel University College of MedicineNeurology, Drexel University College of MedicineSchool of Biomedical Engineering, Science & Health Systems, Drexel UniversityPharmacology & Physiology, Drexel University College of MedicineAbstract 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.http://link.springer.com/article/10.1186/s12967-019-1833-3Plasma exchangeExosomesmiRNAInflammationBiomarker |
| spellingShingle | Sujay Ramanathan Sabrina R. Douglas Guillermo M. Alexander Botros B. Shenoda James E. Barrett Enrique Aradillas Ahmet Sacan Seena K. Ajit Exosome microRNA signatures in patients with complex regional pain syndrome undergoing plasma exchange Journal of Translational Medicine Plasma exchange Exosomes miRNA Inflammation Biomarker |
| title | Exosome microRNA signatures in patients with complex regional pain syndrome undergoing plasma exchange |
| title_full | Exosome microRNA signatures in patients with complex regional pain syndrome undergoing plasma exchange |
| title_fullStr | Exosome microRNA signatures in patients with complex regional pain syndrome undergoing plasma exchange |
| title_full_unstemmed | Exosome microRNA signatures in patients with complex regional pain syndrome undergoing plasma exchange |
| title_short | Exosome microRNA signatures in patients with complex regional pain syndrome undergoing plasma exchange |
| title_sort | exosome microrna signatures in patients with complex regional pain syndrome undergoing plasma exchange |
| topic | Plasma exchange Exosomes miRNA Inflammation Biomarker |
| url | http://link.springer.com/article/10.1186/s12967-019-1833-3 |
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