Initiation of hepatic stellate cell activation extends into chronic liver disease

Abstract Activated hepatic stellate cells (aHSC) are the main source of extra cellular matrix in liver fibrosis. Activation is classically divided in two phases: initiation and perpetuation. Currently, HSC-based therapeutic candidates largely focus on targeting the aHSCs in the perpetuation phase. H...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Vincent De Smet, Nathalie Eysackers, Vincent Merens, Mina Kazemzadeh Dastjerd, Georg Halder, Stefaan Verhulst, Inge Mannaerts, Leo A. van Grunsven
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/8ea65b2a9036464990e291a1c81feff9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8ea65b2a9036464990e291a1c81feff9
record_format	dspace
spelling	oai:doaj.org-article:8ea65b2a9036464990e291a1c81feff92021-11-28T12:04:23ZInitiation of hepatic stellate cell activation extends into chronic liver disease10.1038/s41419-021-04377-12041-4889https://doaj.org/article/8ea65b2a9036464990e291a1c81feff92021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04377-1https://doaj.org/toc/2041-4889Abstract Activated hepatic stellate cells (aHSC) are the main source of extra cellular matrix in liver fibrosis. Activation is classically divided in two phases: initiation and perpetuation. Currently, HSC-based therapeutic candidates largely focus on targeting the aHSCs in the perpetuation phase. However, the importance of HSC initiation during chronic liver disease (CLD) remains unclear. Here, we identified transcriptional programs of initiating and activated HSCs by RNA sequencing, using in vitro and in vivo mouse models of fibrosis. Importantly, we show that both programs are active in HSCs during murine and human CLD. In human cirrhotic livers, scar associated mesenchymal cells employ both transcriptional programs at the single cell level. Our results indicate that the transcriptional programs that drive the initiation of HSCs are still active in humans suffering from CLD. We conclude that molecules involved in the initiation of HSC activation, or in the maintenance of aHSCs can be considered equally important in the search for druggable targets of chronic liver disease.Vincent De SmetNathalie EysackersVincent MerensMina Kazemzadeh DastjerdGeorg HalderStefaan VerhulstInge MannaertsLeo A. van GrunsvenNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 12, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Vincent De Smet Nathalie Eysackers Vincent Merens Mina Kazemzadeh Dastjerd Georg Halder Stefaan Verhulst Inge Mannaerts Leo A. van Grunsven Initiation of hepatic stellate cell activation extends into chronic liver disease
description	Abstract Activated hepatic stellate cells (aHSC) are the main source of extra cellular matrix in liver fibrosis. Activation is classically divided in two phases: initiation and perpetuation. Currently, HSC-based therapeutic candidates largely focus on targeting the aHSCs in the perpetuation phase. However, the importance of HSC initiation during chronic liver disease (CLD) remains unclear. Here, we identified transcriptional programs of initiating and activated HSCs by RNA sequencing, using in vitro and in vivo mouse models of fibrosis. Importantly, we show that both programs are active in HSCs during murine and human CLD. In human cirrhotic livers, scar associated mesenchymal cells employ both transcriptional programs at the single cell level. Our results indicate that the transcriptional programs that drive the initiation of HSCs are still active in humans suffering from CLD. We conclude that molecules involved in the initiation of HSC activation, or in the maintenance of aHSCs can be considered equally important in the search for druggable targets of chronic liver disease.
format	article
author	Vincent De Smet Nathalie Eysackers Vincent Merens Mina Kazemzadeh Dastjerd Georg Halder Stefaan Verhulst Inge Mannaerts Leo A. van Grunsven
author_facet	Vincent De Smet Nathalie Eysackers Vincent Merens Mina Kazemzadeh Dastjerd Georg Halder Stefaan Verhulst Inge Mannaerts Leo A. van Grunsven
author_sort	Vincent De Smet
title	Initiation of hepatic stellate cell activation extends into chronic liver disease
title_short	Initiation of hepatic stellate cell activation extends into chronic liver disease
title_full	Initiation of hepatic stellate cell activation extends into chronic liver disease
title_fullStr	Initiation of hepatic stellate cell activation extends into chronic liver disease
title_full_unstemmed	Initiation of hepatic stellate cell activation extends into chronic liver disease
title_sort	initiation of hepatic stellate cell activation extends into chronic liver disease
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/8ea65b2a9036464990e291a1c81feff9
work_keys_str_mv	AT vincentdesmet initiationofhepaticstellatecellactivationextendsintochronicliverdisease AT nathalieeysackers initiationofhepaticstellatecellactivationextendsintochronicliverdisease AT vincentmerens initiationofhepaticstellatecellactivationextendsintochronicliverdisease AT minakazemzadehdastjerd initiationofhepaticstellatecellactivationextendsintochronicliverdisease AT georghalder initiationofhepaticstellatecellactivationextendsintochronicliverdisease AT stefaanverhulst initiationofhepaticstellatecellactivationextendsintochronicliverdisease AT ingemannaerts initiationofhepaticstellatecellactivationextendsintochronicliverdisease AT leoavangrunsven initiationofhepaticstellatecellactivationextendsintochronicliverdisease
_version_	1718408211689635840

Initiation of hepatic stellate cell activation extends into chronic liver disease

Ejemplares similares