HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal

Abstract Peritoneal fibrosis is a pathological alteration of the peritoneal membrane occurring in a variety of conditions including peritoneal dialysis (PD), post-surgery adhesions and peritoneal metastases. The acquisition of invasive and pro-fibrotic abilities by mesothelial cells (MCs) through in...

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Autores principales:	Lucia Rossi, Cecilia Battistelli, Valeria de Turris, Valeria Noce, Clemens Zwergel, Sergio Valente, Alessandra Moioli, Andrea Manzione, Marco Palladino, Veronica Bordoni, Alessandro Domenici, Paolo Menè, Antonello Mai, Marco Tripodi, Raffaele Strippoli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/456c8846a24d43e285fe7f27625f205f
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spelling	oai:doaj.org-article:456c8846a24d43e285fe7f27625f205f2021-12-02T15:08:17ZHDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal10.1038/s41598-018-26319-22045-2322https://doaj.org/article/456c8846a24d43e285fe7f27625f205f2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-26319-2https://doaj.org/toc/2045-2322Abstract Peritoneal fibrosis is a pathological alteration of the peritoneal membrane occurring in a variety of conditions including peritoneal dialysis (PD), post-surgery adhesions and peritoneal metastases. The acquisition of invasive and pro-fibrotic abilities by mesothelial cells (MCs) through induction of MMT, a cell-specific form of EMT, plays a main role in this process. Aim of this study was to evaluate possible effects of histone deacetylase (HDAC) inhibitors, key components of the epigenetic machinery, in counteracting MMT observed in MCs isolated from effluent of PD patients. HDAC inhibitors with different class/isoform selectivity have been used for pharmacological inhibition. While the effect of other inhibitors was limited to a partial E-cadherin re-expression, MS-275, a HDAC1-3 inhibitor, promoted: (i) downregulation of mesenchymal markers (MMP2, Col1A1, PAI-1, TGFβ1, TGFβRI) (ii) upregulation of epithelial markers (E-cadherin, Occludin), (iii) reacquisition of an epithelial-like morphology and (iv) marked reduction of cellular invasiveness. Results were confirmed by HDAC1 genetic silencing. Mechanistically, MS-275 causes: (i) increase of nuclear histone H3 acetylation (ii) rescue of the acetylation profile on E-cadherin promoter, (iii) Snail functional impairment. Overall, our study, pinpointing a role for HDAC1, revealed a new player in the regulation of peritoneal fibrosis, providing the rationale for future therapeutic opportunities.Lucia RossiCecilia BattistelliValeria de TurrisValeria NoceClemens ZwergelSergio ValenteAlessandra MoioliAndrea ManzioneMarco PalladinoVeronica BordoniAlessandro DomeniciPaolo MenèAntonello MaiMarco TripodiRaffaele StrippoliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lucia Rossi Cecilia Battistelli Valeria de Turris Valeria Noce Clemens Zwergel Sergio Valente Alessandra Moioli Andrea Manzione Marco Palladino Veronica Bordoni Alessandro Domenici Paolo Menè Antonello Mai Marco Tripodi Raffaele Strippoli HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal
description	Abstract Peritoneal fibrosis is a pathological alteration of the peritoneal membrane occurring in a variety of conditions including peritoneal dialysis (PD), post-surgery adhesions and peritoneal metastases. The acquisition of invasive and pro-fibrotic abilities by mesothelial cells (MCs) through induction of MMT, a cell-specific form of EMT, plays a main role in this process. Aim of this study was to evaluate possible effects of histone deacetylase (HDAC) inhibitors, key components of the epigenetic machinery, in counteracting MMT observed in MCs isolated from effluent of PD patients. HDAC inhibitors with different class/isoform selectivity have been used for pharmacological inhibition. While the effect of other inhibitors was limited to a partial E-cadherin re-expression, MS-275, a HDAC1-3 inhibitor, promoted: (i) downregulation of mesenchymal markers (MMP2, Col1A1, PAI-1, TGFβ1, TGFβRI) (ii) upregulation of epithelial markers (E-cadherin, Occludin), (iii) reacquisition of an epithelial-like morphology and (iv) marked reduction of cellular invasiveness. Results were confirmed by HDAC1 genetic silencing. Mechanistically, MS-275 causes: (i) increase of nuclear histone H3 acetylation (ii) rescue of the acetylation profile on E-cadherin promoter, (iii) Snail functional impairment. Overall, our study, pinpointing a role for HDAC1, revealed a new player in the regulation of peritoneal fibrosis, providing the rationale for future therapeutic opportunities.
format	article
author	Lucia Rossi Cecilia Battistelli Valeria de Turris Valeria Noce Clemens Zwergel Sergio Valente Alessandra Moioli Andrea Manzione Marco Palladino Veronica Bordoni Alessandro Domenici Paolo Menè Antonello Mai Marco Tripodi Raffaele Strippoli
author_facet	Lucia Rossi Cecilia Battistelli Valeria de Turris Valeria Noce Clemens Zwergel Sergio Valente Alessandra Moioli Andrea Manzione Marco Palladino Veronica Bordoni Alessandro Domenici Paolo Menè Antonello Mai Marco Tripodi Raffaele Strippoli
author_sort	Lucia Rossi
title	HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal
title_short	HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal
title_full	HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal
title_fullStr	HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal
title_full_unstemmed	HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal
title_sort	hdac1 inhibition by ms-275 in mesothelial cells limits cellular invasion and promotes mmt reversal
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/456c8846a24d43e285fe7f27625f205f
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HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal

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