Class II HDAC inhibition hampers hepatic stellate cell activation by induction of microRNA-29.

<h4>Background</h4>The conversion of a quiescent vitamin A storing hepatic stellate cell (HSC) to a matrix producing, contractile myofibroblast-like activated HSC is a key event in the onset of liver disease following injury of any aetiology. Previous studies have shown that class I hist...

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Autores principales:	Inge Mannaerts, Nathalie Eysackers, Oscar O Onyema, Katrien Van Beneden, Sergio Valente, Antonello Mai, Margarete Odenthal, Leo A van Grunsven
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6144dd832fc24bf0a35956ebb8b9d756
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spelling	oai:doaj.org-article:6144dd832fc24bf0a35956ebb8b9d7562021-11-18T07:59:04ZClass II HDAC inhibition hampers hepatic stellate cell activation by induction of microRNA-29.1932-620310.1371/journal.pone.0055786https://doaj.org/article/6144dd832fc24bf0a35956ebb8b9d7562013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23383282/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The conversion of a quiescent vitamin A storing hepatic stellate cell (HSC) to a matrix producing, contractile myofibroblast-like activated HSC is a key event in the onset of liver disease following injury of any aetiology. Previous studies have shown that class I histone deacetylases (HDACs) are involved in the phenotypical changes occurring during stellate cell activation in liver and pancreas.<h4>Aims</h4>In the current study we investigate the role of class II HDACs during HSC activation.<h4>Methods</h4>We characterized the expression of the class II HDACs freshly isolated mouse HSCs. We inhibited HDAC activity by selective pharmacological inhibition with MC1568, and by repressing class II HDAC gene expression using specific siRNAs.<h4>Results</h4>Inhibition of HDAC activity leads to a strong reduction of HSC activation markers α-SMA, lysyl oxidase and collagens as well as an inhibition of cell proliferation. Knock down experiments showed that HDAC4 contributes to HSC activation by regulating lysyl oxidase expression. In addition, we observed a strong up regulation of miR-29, a well-known anti-fibrotic miR, upon treatment with MC1568. Our in vivo work suggests that a successful inhibition of class II HDACs could be promising for development of future anti-fibrotic compounds.<h4>Conclusions</h4>In conclusion, the use of MC1568 has enabled us to identify a role for class II HDACs regulating miR-29 during HSC activation.Inge MannaertsNathalie EysackersOscar O OnyemaKatrien Van BenedenSergio ValenteAntonello MaiMargarete OdenthalLeo A van GrunsvenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e55786 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Inge Mannaerts Nathalie Eysackers Oscar O Onyema Katrien Van Beneden Sergio Valente Antonello Mai Margarete Odenthal Leo A van Grunsven Class II HDAC inhibition hampers hepatic stellate cell activation by induction of microRNA-29.
description	<h4>Background</h4>The conversion of a quiescent vitamin A storing hepatic stellate cell (HSC) to a matrix producing, contractile myofibroblast-like activated HSC is a key event in the onset of liver disease following injury of any aetiology. Previous studies have shown that class I histone deacetylases (HDACs) are involved in the phenotypical changes occurring during stellate cell activation in liver and pancreas.<h4>Aims</h4>In the current study we investigate the role of class II HDACs during HSC activation.<h4>Methods</h4>We characterized the expression of the class II HDACs freshly isolated mouse HSCs. We inhibited HDAC activity by selective pharmacological inhibition with MC1568, and by repressing class II HDAC gene expression using specific siRNAs.<h4>Results</h4>Inhibition of HDAC activity leads to a strong reduction of HSC activation markers α-SMA, lysyl oxidase and collagens as well as an inhibition of cell proliferation. Knock down experiments showed that HDAC4 contributes to HSC activation by regulating lysyl oxidase expression. In addition, we observed a strong up regulation of miR-29, a well-known anti-fibrotic miR, upon treatment with MC1568. Our in vivo work suggests that a successful inhibition of class II HDACs could be promising for development of future anti-fibrotic compounds.<h4>Conclusions</h4>In conclusion, the use of MC1568 has enabled us to identify a role for class II HDACs regulating miR-29 during HSC activation.
format	article
author	Inge Mannaerts Nathalie Eysackers Oscar O Onyema Katrien Van Beneden Sergio Valente Antonello Mai Margarete Odenthal Leo A van Grunsven
author_facet	Inge Mannaerts Nathalie Eysackers Oscar O Onyema Katrien Van Beneden Sergio Valente Antonello Mai Margarete Odenthal Leo A van Grunsven
author_sort	Inge Mannaerts
title	Class II HDAC inhibition hampers hepatic stellate cell activation by induction of microRNA-29.
title_short	Class II HDAC inhibition hampers hepatic stellate cell activation by induction of microRNA-29.
title_full	Class II HDAC inhibition hampers hepatic stellate cell activation by induction of microRNA-29.
title_fullStr	Class II HDAC inhibition hampers hepatic stellate cell activation by induction of microRNA-29.
title_full_unstemmed	Class II HDAC inhibition hampers hepatic stellate cell activation by induction of microRNA-29.
title_sort	class ii hdac inhibition hampers hepatic stellate cell activation by induction of microrna-29.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6144dd832fc24bf0a35956ebb8b9d756
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Class II HDAC inhibition hampers hepatic stellate cell activation by induction of microRNA-29.

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