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Initiation of hepatic stellate cell activation extends into chronic liver disease

Authors :
Georg Halder
Nathalie Eysackers
Inge Mannaerts
Stefaan Verhulst
Leo A. van Grunsven
Mina Kazemzadeh Dastjerd
Vincent Merens
Vincent De Smet
Faculty of Medicine and Pharmacy
Liver Cell Biology
Basic (bio-) Medical Sciences
Internal Medicine
Translational Liver Cell Biology
Source :
Cell Death and Disease, Vol 12, Iss 12, Pp 1-10 (2021), Cell Death & Disease
Publication Year :
2021
Publisher :
Nature Publishing Group, 2021.

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. ispartof: CELL DEATH & DISEASE vol:12 issue:12 ispartof: location:England status: published

Details

Language :
English
ISSN :
20414889
Volume :
12
Issue :
12
Database :
OpenAIRE
Journal :
Cell Death and Disease
Accession number :
edsair.doi.dedup.....922aa3d718553c5051ca021cc8b3040b