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

Marina Barcena-Varela, Leticia Colyn, Maite G. Fernandez-Barrena

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations

Abstract

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.

Original languageEnglish
Article number2507
JournalInternational Journal of Molecular Sciences
Volume20
Issue number10
DOIs
StatePublished - 2 May 2019
Externally publishedYes

Keywords

  • Epigenetic remodeling
  • Fibrosis
  • Hepatic stellate cells
  • Tumor microenvironment

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