ArticleJournal of hepatology2016
Hepatic stellate cell transdifferentiation involves genome-wide remodeling of the DNA methylation landscape.
Article in Journal of hepatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 129 citations in OpenAlex.
- HCV patients with residual fibrosis after DAA treatment re-establish their epigenetic signature after prolonged-release pirfenidone: MINERVA study.Clinical epigenetics · 2025Trial
- Precision pathophysiology in steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Gandouling protects against hepatic fibrosis in Wilson disease through the lncRNA-SNHG7/miR-29b/DNMT3A pathway.3 Biotech · 2026Article
- <p>Beyond hepatic stellate cell heterogeneity: Resolving fibrosis, restoring regeneration (Review)</p>.International journal of molecular medicine · 2026Review
- Epigenetic reprogramming of hepatic antigen presenting cells in chronic liver disease.Frontiers in immunology · 2026Review
- Folate deficiency correlates with severity of primary biliary cholangitis via modulating key regulatory genes.Frontiers in nutrition · 2026Article
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Metabolic Sparks in the Liver: Metabolic and Epigenetic Reprogramming in Hepatic Stellate Cells Activation and Its Implications for Human Metabolic Diseases.Diabetes & metabolism journal · 2025Review
- Liver TET1 promotes metabolic dysfunction-associated steatotic liver disease.EMBO molecular medicine · 2025Article
- Association Between Active DNA Demethylation and Liver Fibrosis in Individuals with Metabolic-Associated Steatotic Liver Disease (MASLD).International journal of molecular sciences · 2025Article
- Deciphering the Role of Oroxylin A in Liver Fibrosis.Drug design, development and therapy · 2025Review
- Clinical and pathological characteristics of metabolic dysfunction-associated steatotic liver disease and the key role of epigenetic regulation: implications for molecular mechanism and treatment.Therapeutic advances in endocrinology and metabolism · 2025Review
- Liver Fibrosis: From Basic Science towards Clinical Progress, Focusing on the Central Role of Hepatic Stellate Cells.International journal of molecular sciences · 2024Review
- Role of Folate in Liver Diseases.Nutrients · 2024Review
- Survivin inhibition ameliorates liver fibrosis by inducing hepatic stellate cell senescence and depleting hepatic macrophage population.Journal of cell communication and signaling · 2024Article
- Epigenetic modification in liver fibrosis: Promising therapeutic direction with significant challenges ahead.Acta pharmaceutica Sinica. B · 2024Review
- Inhibition of DNMT3B expression in activated hepatic stellate cells overcomes chemoresistance in the tumor microenvironment of hepatocellular carcinoma.Scientific reports · 2024Article
- Emerging role of lipophagy in liver disorders.Molecular and cellular biochemistry · 2024Review
- Exportin 4 DNA promoter methylation in liver fibrosis.PloS one · 2024Article
- DNA 5mC and RNA mCell death and differentiation · 2023Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsDNA methylation (5-mC) is an epigenetic mark that is an established regulator of transcriptional repression with an important role in liver fibrosis. Currently, there is very little knowledge available as to how DNA methylation controls the phenotype of hepatic stellate cell (HSC), the key cell type responsible for onset and progression of liver fibrosis. Moreover, recently discovered DNA hydroxymethylation (5-hmC) is involved in transcriptional activation and its patterns are often altered in human diseases. The aim of this study is to investigate the role of DNA methylation/hydroxymethylation in liver fibrosis.
methodsLevels of 5-mC and 5-hmC were assessed by slot blot in a range of animal liver fibrosis models and human liver diseases. Expression levels of TET and DNMT enzymes were measured by qRT-PCR and Western blotting. Reduced representation bisulfite sequencing (RRBS) method was used to examine 5-mC and 5-hmC patterns in quiescent and in vivo activated rat HSC.
resultsWe demonstrate global alteration in 5-mC and 5-hmC and their regulatory enzymes that accompany liver fibrosis and HSC transdifferentiation. Using RRBS, we show exact genomic positions of changed methylation patterns in quiescent and in vivo activated rat HSC. In addition, we demonstrate that reduction in DNMT3a expression leads to attenuation of pro-fibrogenic phenotype in activated HSC.
conclusionsOur data suggest that DNA 5-mC/5-hmC is a crucial step in HSC activation and therefore fibrogenesis. Changes in DNA methylation during HSC activation may bring new insights into the molecular events underpinning fibrogenesis and may provide biomarkers for disease progression as well as potential new drug targets.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.