Epigenetic mechanisms in hepatic stellate cell activation during liver fibrosis and carcinogenesis

Liver fibrosis is an essential component of chronic liver disease (CLD) and hepatocarcinogenesis. The fibrotic stroma is a consequence of sustained liver damage combined with exacerbated extracellular matrix (ECM) accumulation. In this context, activation of hepatic stellate cells (HSCs) plays a key...

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Bibliographic Details
Authors: Bárcena-Varela, M. (Marina)|||/items/f0c99950-fb04-4dad-80d8-e7c15973758b, Colyn, L. (Leticia)|||/items/5972aa59-9877-442f-b405-1d4af39847db, García-Fernández-de-Barrena, M. (Maite)|||/items/cfa77580-40b9-43a4-b237-b234ef7fb6cb
Format: article
Publication Date:2019
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/62299
Online Access:https://hdl.handle.net/10171/62299
Access Level:Open access
Keyword:Tumor microenvironment
Fibrosis
Hepatic stellate cells
Epigenetic remodeling
Description
Summary:Liver fibrosis is an essential component of chronic liver disease (CLD) and hepatocarcinogenesis. The fibrotic stroma is a consequence of sustained liver damage combined with exacerbated extracellular matrix (ECM) accumulation. In this context, activation of hepatic stellate cells (HSCs) plays a key role in both initiation and perpetuation of fibrogenesis. These cells suffer profound remodeling of gene expression in this process. This review is focused on the epigenetic alterations participating in the transdifferentiation of HSCs from the quiescent to activated state. Recent advances in the field of DNA methylation and post-translational modifications (PTM) of histones (acetylation and methylation) patterns are discussed here, together with altered expression and activity of epigenetic remodelers. We also consider recent advances in translational approaches, including the use of epigenetic marks as biomarkers and the promising antifibrotic properties of epigenetic drugs that are currently being used in patients.