ArticleJournal of hepatology2022
Histone acetylation of bile acid transporter genes plays a critical role in cirrhosis.
Article in Journal of hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Predictive value of serum bile acids as metabolite biomarkers for liver cirrhosis: a systematic review and meta-analysis.Metabolomics : Official journal of the Metabolomic Society · 2022Pooled it
- FXR-YAP signalling maintains biliary epithelial cell identity and preserves liver homeostasis.Nature metabolism · 2026Article
- FXR's double life in bile ducts.Nature metabolism · 2026Article
- Sialic acid-guided spatiotemporal hydrogel therapy for liver cancer.Materials today. Bio · 2026Article
- H3K9 acetylation-dependent CHAC1 transcription in dihydroartemisinin-induced hepatic stellate cell ferroptosis.Chinese medical journal · 2026Article
- Post-Translational Modifications of Histones and Non-Histones in Liver Disease and Traditional Chinese Medicine Treatment: A Narrative Review.Pharmacogenomics and personalized medicine · 2026Review
- The importance of sex dimorphism in liver metabolism and progressive liver diseases.Biology of sex differences · 2025Review
- KANSL3 directs transcriptional programs essential for hepatic metabolism and differentiation.Life science alliance · 2025Article
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
- Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease.JHEP reports : innovation in hepatology · 2025Review
- Glutamate as a therapeutic strategy to promote liver regeneration.Clinical and translational medicine · 2025Article
- Microbiota, mitochondria, and epigenetics in health and disease: converging pathways to solve the puzzle.Pflugers Archiv : European journal of physiology · 2025Review
- Article
- Metabolism of hepatic stellate cells in chronic liver diseases: emerging molecular and therapeutic interventions.Theranostics · 2025Review
- The loss of hepatitis B virus receptor NTCP/SLC10A1 in human liver cancer cells is due to epigenetic silencing.Journal of virology · 2024Article
- Infection‑associated bile acid disturbance contributes to macrophage activation in patients with cirrhosis.Molecular medicine reports · 2024Article
- Article
- Differential contribution for ERK1 and ERK2 kinases in BRAFCell death and differentiation · 2024Article
- Cold exposure reinstates NADCell stress · 2024Article
- Mcrs1 regulates G2/M transition and spindle assembly during mouse oocyte meiosis.EMBO reports · 2023Article
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsOwing to the lack of genetic animal models that adequately recreate key clinical characteristics of cirrhosis, the molecular pathogenesis of cirrhosis has been poorly characterized, and treatments remain limited. Hence, we aimed to better elucidate the pathological mechanisms of cirrhosis using a novel murine model.
methodsWe report on the first murine genetic model mimicking human cirrhosis induced by hepatocyte-specific elimination of microspherule protein 1 (MCRS1), a member of non-specific lethal (NSL) and INO80 chromatin-modifier complexes. Using this genetic tool with other mouse models, cell culture and human samples, combined with quantitative proteomics, single nuclei/cell RNA sequencing and chromatin immunoprecipitation assays, we investigated mechanisms of cirrhosis.
resultsMCRS1 loss in mouse hepatocytes modulates the expression of bile acid (BA) transporters - with a pronounced downregulation of Na
conclusionsOur data reveal a previously unrecognized function of MCRS1 as a critical histone acetylation regulator, maintaining gene expression and liver homeostasis. MCRS1 loss induces acetylation of BA transporter genes, perturbation of BA flow, and consequently, FXR activation in HSCs. This axis represents a central and universal signaling event in cirrhosis, which has significant implications for cirrhosis treatment. LAY SUMMARY: By genetic ablation of MCRS1 in mouse hepatocytes, we generate the first genetic mouse model of cirrhosis that recapitulates human features. Herein, we demonstrate that the activation of the bile acid/FXR axis in liver fibroblasts is key in cirrhosis development.
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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.