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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/7/1117
_version_ 1827624104480473088
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.
first_indexed 2024-03-09T12:01:09Z
format Article
id doaj.art-decebf8dd0144306a5406408ed158800
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-09T12:01:09Z
publishDate 2022-03-01
publisher MDPI AG
record_format Article
series Cells
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
work_keys_str_mv AT sarabozzini mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT claudiadelfante mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT monicamorosini mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT haticeoyaberezhinskiy mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT sophiaauner mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT elenacattaneo mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT matteodellazoppa mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT laurapandolfi mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT rosaliacacciatore mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT cesareperotti mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT konradhoetzenecker mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT peterjaksch mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT albertobenazzo mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas
AT federicameloni mechanismsofactionofextracorporealphotopheresisinthecontrolofbronchiolitisobliteranssyndromebosinvolvementofcirculatingmirnas