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...

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Main Authors:	Serena Vella, Pier Giulio Conaldi, Emanuela Cova, Federica Meloni, Rosa Liotta, Salvatore Cuzzocrea, Lavinia Martino, Alessandro Bertani, Angelo Luca, Patrizio Vitulo
Format:	article
Language:	EN
Published:	Nature Portfolio 2018
Subjects:	Medicine R Science Q
Online Access:	https://doaj.org/article/42b1010b154e4e2f804bbd54ef3d9cd0
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spelling	oai:doaj.org-article:42b1010b154e4e2f804bbd54ef3d9cd02021-12-02T15:08:50ZLung resident mesenchymal cells isolated from patients with the Bronchiolitis Obliterans Syndrome display a deregulated epigenetic profile10.1038/s41598-018-29504-52045-2322https://doaj.org/article/42b1010b154e4e2f804bbd54ef3d9cd02018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29504-5https://doaj.org/toc/2045-2322Abstract 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.Serena VellaPier Giulio ConaldiEmanuela CovaFederica MeloniRosa LiottaSalvatore CuzzocreaLavinia MartinoAlessandro BertaniAngelo LucaPatrizio VituloNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Serena Vella Pier Giulio Conaldi Emanuela Cova Federica Meloni Rosa Liotta Salvatore Cuzzocrea Lavinia Martino Alessandro Bertani Angelo Luca Patrizio Vitulo Lung resident mesenchymal cells isolated from patients with the Bronchiolitis Obliterans Syndrome display a deregulated epigenetic profile
description	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.
format	article
author	Serena Vella Pier Giulio Conaldi Emanuela Cova Federica Meloni Rosa Liotta Salvatore Cuzzocrea Lavinia Martino Alessandro Bertani Angelo Luca Patrizio Vitulo
author_facet	Serena Vella Pier Giulio Conaldi Emanuela Cova Federica Meloni Rosa Liotta Salvatore Cuzzocrea Lavinia Martino Alessandro Bertani Angelo Luca Patrizio Vitulo
author_sort	Serena Vella
title	Lung resident mesenchymal cells isolated from patients with the Bronchiolitis Obliterans Syndrome display a deregulated epigenetic profile
title_short	Lung resident mesenchymal cells isolated from patients with the Bronchiolitis Obliterans Syndrome display a deregulated epigenetic profile
title_full	Lung resident mesenchymal cells isolated from patients with the Bronchiolitis Obliterans Syndrome display a deregulated epigenetic profile
title_fullStr	Lung resident mesenchymal cells isolated from patients with the Bronchiolitis Obliterans Syndrome display a deregulated epigenetic profile
title_full_unstemmed	Lung resident mesenchymal cells isolated from patients with the Bronchiolitis Obliterans Syndrome display a deregulated epigenetic profile
title_sort	lung resident mesenchymal cells isolated from patients with the bronchiolitis obliterans syndrome display a deregulated epigenetic profile
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/42b1010b154e4e2f804bbd54ef3d9cd0
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Lung resident mesenchymal cells isolated from patients with the Bronchiolitis Obliterans Syndrome display a deregulated epigenetic profile

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