Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs
Clinical evidence suggests an improvement or stabilization of lung function in a fraction of patients with bronchiolitis obliterans syndrome (BOS) treated by extracorporeal photopheresis (ECP); however, few studies have explored the epigenetic and molecular regulation of this therapy. The aim of pre...
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2022-03-01
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author | Sara Bozzini Claudia Del Fante Monica Morosini Hatice Oya Berezhinskiy Sophia Auner Elena Cattaneo Matteo Della Zoppa Laura Pandolfi Rosalia Cacciatore Cesare Perotti Konrad Hoetzenecker Peter Jaksch Alberto Benazzo Federica Meloni |
author_facet | Sara Bozzini Claudia Del Fante Monica Morosini Hatice Oya Berezhinskiy Sophia Auner Elena Cattaneo Matteo Della Zoppa Laura Pandolfi Rosalia Cacciatore Cesare Perotti Konrad Hoetzenecker Peter Jaksch Alberto Benazzo Federica Meloni |
author_sort | Sara Bozzini |
collection | DOAJ |
description | Clinical evidence suggests an improvement or stabilization of lung function in a fraction of patients with bronchiolitis obliterans syndrome (BOS) treated by extracorporeal photopheresis (ECP); however, few studies have explored the epigenetic and molecular regulation of this therapy. The aim of present study was to evaluate whether a specific set of miRNAs were significantly regulated by ECP. Total RNA was isolated from serum of patients with established BOS grade 1–2 prior to the start and after 6 months of ECP treatment. We observed a significant downregulation of circulating hsa-miR-155-5p, hsa-miR-146a-5p and hsa-miR-31-5p in BOS patients at the start of ECP when compared to healthy subjects. In responders, increased miR-155-5p and decreased miR-23b-3p expression levels at 6 months were found. SMAD4 mRNA was found to be a common target of these two miRNAs in prediction pathways analysis, and a significant downregulation was found at 6 months in PBMCs of a subgroup of ECP-treated patients. According to previous evidence, the upregulation of miR-155 might be correlated with a pro-tolerogenic modulation of the immune system. Our analysis also suggests that SMAD4 might be a possible target for miR-155-5p. Further longitudinal studies are needed to address the possible role of miR-155 and its downstream targets. |
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spelling | doaj.art-decebf8dd0144306a5406408ed1588002023-11-30T23:03:43ZengMDPI AGCells2073-44092022-03-01117111710.3390/cells11071117Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAsSara Bozzini0Claudia Del Fante1Monica Morosini2Hatice Oya Berezhinskiy3Sophia Auner4Elena Cattaneo5Matteo Della Zoppa6Laura Pandolfi7Rosalia Cacciatore8Cesare Perotti9Konrad Hoetzenecker10Peter Jaksch11Alberto Benazzo12Federica Meloni13Laboratory of Respiratory Disease, Cell Biology Section, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyImmunohaematology and Transfusion Service, Apheresis and Cell Therapy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyLaboratory of Respiratory Disease, Cell Biology Section, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Wien, AustriaDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Wien, AustriaLaboratory of Respiratory Disease, Cell Biology Section, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyLaboratory of Respiratory Disease, Cell Biology Section, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyLaboratory of Respiratory Disease, Cell Biology Section, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyImmunohaematology and Transfusion Service, Apheresis and Cell Therapy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyImmunohaematology and Transfusion Service, Apheresis and Cell Therapy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Wien, AustriaDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Wien, AustriaDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Wien, AustriaUOS Transplant Center, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyClinical evidence suggests an improvement or stabilization of lung function in a fraction of patients with bronchiolitis obliterans syndrome (BOS) treated by extracorporeal photopheresis (ECP); however, few studies have explored the epigenetic and molecular regulation of this therapy. The aim of present study was to evaluate whether a specific set of miRNAs were significantly regulated by ECP. Total RNA was isolated from serum of patients with established BOS grade 1–2 prior to the start and after 6 months of ECP treatment. We observed a significant downregulation of circulating hsa-miR-155-5p, hsa-miR-146a-5p and hsa-miR-31-5p in BOS patients at the start of ECP when compared to healthy subjects. In responders, increased miR-155-5p and decreased miR-23b-3p expression levels at 6 months were found. SMAD4 mRNA was found to be a common target of these two miRNAs in prediction pathways analysis, and a significant downregulation was found at 6 months in PBMCs of a subgroup of ECP-treated patients. According to previous evidence, the upregulation of miR-155 might be correlated with a pro-tolerogenic modulation of the immune system. Our analysis also suggests that SMAD4 might be a possible target for miR-155-5p. Further longitudinal studies are needed to address the possible role of miR-155 and its downstream targets.https://www.mdpi.com/2073-4409/11/7/1117circulating microRNAsBOSECP |
spellingShingle | Sara Bozzini Claudia Del Fante Monica Morosini Hatice Oya Berezhinskiy Sophia Auner Elena Cattaneo Matteo Della Zoppa Laura Pandolfi Rosalia Cacciatore Cesare Perotti Konrad Hoetzenecker Peter Jaksch Alberto Benazzo Federica Meloni Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs Cells circulating microRNAs BOS ECP |
title | Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs |
title_full | Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs |
title_fullStr | Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs |
title_full_unstemmed | Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs |
title_short | Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs |
title_sort | mechanisms of action of extracorporeal photopheresis in the control of bronchiolitis obliterans syndrome bos involvement of circulating mirnas |
topic | circulating microRNAs BOS ECP |
url | https://www.mdpi.com/2073-4409/11/7/1117 |
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