Lung resident mesenchymal cells isolated from patients with the Bronchiolitis Obliterans Syndrome display a deregulated epigenetic profile

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Abstract

Bronchiolitis Obliterans Syndrome is the major determinant of the graft function loss after lung transplantation, but its pathogenesis is still incompletely understood and currently available therapeutic strategies are poorly effective. A deeper understanding of its pathogenic mechanisms is crucial for the development of new strategies to prevent and treat this devastating complication. In this study, we focused on the mesenchymal stromal cells, recently recognized as BOS key effectors, and our primary aim was to identify their epigenetic determinants, such as histone modifications and non-coding RNA regulation, which could contribute to their differentiation in myofibroblasts. Interestingly, we identified a deregulated expression of histone deacetylases and methyltransferases, and a microRNA-epigenetic regulatory network, which could represent novel targets for anti-fibrotic therapy. We validated our results in vitro, in a cell model of fibrogenesis, confirming the epigenetic involvement in this process and paving the way for a new application for epigenetic drugs.
Original languageEnglish
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Bronchiolitis Obliterans
Epigenomics
Lung
Histone Code
Untranslated RNA
Histone Deacetylases
Myofibroblasts
Lung Transplantation
MicroRNAs
Mesenchymal Stromal Cells
Transplants
Therapeutics
Pharmaceutical Preparations

Cite this

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title = "Lung resident mesenchymal cells isolated from patients with the Bronchiolitis Obliterans Syndrome display a deregulated epigenetic profile",
abstract = "Bronchiolitis Obliterans Syndrome is the major determinant of the graft function loss after lung transplantation, but its pathogenesis is still incompletely understood and currently available therapeutic strategies are poorly effective. A deeper understanding of its pathogenic mechanisms is crucial for the development of new strategies to prevent and treat this devastating complication. In this study, we focused on the mesenchymal stromal cells, recently recognized as BOS key effectors, and our primary aim was to identify their epigenetic determinants, such as histone modifications and non-coding RNA regulation, which could contribute to their differentiation in myofibroblasts. Interestingly, we identified a deregulated expression of histone deacetylases and methyltransferases, and a microRNA-epigenetic regulatory network, which could represent novel targets for anti-fibrotic therapy. We validated our results in vitro, in a cell model of fibrogenesis, confirming the epigenetic involvement in this process and paving the way for a new application for epigenetic drugs.",
author = "Serena Vella and Conaldi, {Pier Giulio} and Emanuela Cova and Federica Meloni and Rosa Liotta and Salvatore Cuzzocrea and Lavinia Martino and Alessandro Bertani and Angelo Luca and Patrizio Vitulo",
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T1 - Lung resident mesenchymal cells isolated from patients with the Bronchiolitis Obliterans Syndrome display a deregulated epigenetic profile

AU - Vella, Serena

AU - Conaldi, Pier Giulio

AU - Cova, Emanuela

AU - Meloni, Federica

AU - Liotta, Rosa

AU - Cuzzocrea, Salvatore

AU - Martino, Lavinia

AU - Bertani, Alessandro

AU - Luca, Angelo

AU - Vitulo, Patrizio

N1 - M1 - 11167

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Bronchiolitis Obliterans Syndrome is the major determinant of the graft function loss after lung transplantation, but its pathogenesis is still incompletely understood and currently available therapeutic strategies are poorly effective. A deeper understanding of its pathogenic mechanisms is crucial for the development of new strategies to prevent and treat this devastating complication. In this study, we focused on the mesenchymal stromal cells, recently recognized as BOS key effectors, and our primary aim was to identify their epigenetic determinants, such as histone modifications and non-coding RNA regulation, which could contribute to their differentiation in myofibroblasts. Interestingly, we identified a deregulated expression of histone deacetylases and methyltransferases, and a microRNA-epigenetic regulatory network, which could represent novel targets for anti-fibrotic therapy. We validated our results in vitro, in a cell model of fibrogenesis, confirming the epigenetic involvement in this process and paving the way for a new application for epigenetic drugs.

AB - Bronchiolitis Obliterans Syndrome is the major determinant of the graft function loss after lung transplantation, but its pathogenesis is still incompletely understood and currently available therapeutic strategies are poorly effective. A deeper understanding of its pathogenic mechanisms is crucial for the development of new strategies to prevent and treat this devastating complication. In this study, we focused on the mesenchymal stromal cells, recently recognized as BOS key effectors, and our primary aim was to identify their epigenetic determinants, such as histone modifications and non-coding RNA regulation, which could contribute to their differentiation in myofibroblasts. Interestingly, we identified a deregulated expression of histone deacetylases and methyltransferases, and a microRNA-epigenetic regulatory network, which could represent novel targets for anti-fibrotic therapy. We validated our results in vitro, in a cell model of fibrogenesis, confirming the epigenetic involvement in this process and paving the way for a new application for epigenetic drugs.

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DO - 10.1038/s41598-018-29504-5

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JO - Scientific Reports

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