ArticleJournal of hepatology2022
Long non-coding RNA ACTA2-AS1 promotes ductular reaction by interacting with the p300/ELK1 complex.
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 33 papers.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
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- Lactate-activated astrocytes promote NSCLC brain metastasis through extracellular vesicle-mediated miR-8085/TRIM67/ELK1 signaling axis.Cellular & molecular biology letters · 2026Article
- Single cell multiomic landscape reveals gene programs driving lipid droplet heterogeneity in hepatic steatosis.Scientific reports · 2026Article
- Epigenetic and post-translational regulatory networks of ferroptosis in the tumor immune microenvironment.Experimental hematology & oncology · 2026Review
- Decoding the ceRNA regulatory landscape: a comprehensive transcriptomic analysis of ncRNA-driven bladder fibrosis following spinal cord injury.Translational andrology and urology · 2025Article
- Mechanisms and targeted prevention of abnormal ductular reaction caused by a low concentration of Benzo(a)pyrene.Cell death & disease · 2025Article
- Novel insights into lncRNAs as key regulators of post-translational modifications in cancer: mechanisms and therapeutic potential.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- EP300/CREBBP induces osteogenic differentiation of valve interstitial cells by promoting the SPP1 expression in calcific aortic valve disease.Cytotechnology · 2025Article
- SMAD3 and p300 complex scaffolding by long non-coding RNA LIMD1-AS1 promotes TGF-β-induced breast cancer cell plasticity.Nucleic acids research · 2025Article
- Aramchol attenuates fibrosis in mouse models of biliary fibrosis and blocks the TGFβ-induced fibroinflammatory mediators in cholangiocytes.Hepatology communications · 2025Article
- Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities.Gastroenterology · 2025Review
- LncRNAs, RNA Therapeutics, and Emerging Technologies in Liver Pathobiology.Seminars in liver disease · 2025Review
- ULK1 methylation promotes TGF-β1-induced endometrial fibrosis via the FOXP1/DNMT1 axis.The Kaohsiung journal of medical sciences · 2025Article
- Multi-omics perspective: mechanisms of gastrointestinal injury repair.Burns & trauma · 2025Review
- Human Amniotic Epithelial Stem Cell Exosomes Regulate Chondrocyte Ferroptosis through ACTA2-AS1-Targeted Binding to ACSL4 for Osteoarthritis Intervention.Research (Washington, D.C.) · 2025Article
- LncRNA-encoded peptides in cancer.Journal of hematology & oncology · 2024Review
- Noncoding RNA-Mediated Epigenetic Regulation in Hepatic Stellate Cells of Liver Fibrosis.Non-coding RNA · 2024Review
- Biliary fibrosis is an important but neglected pathological feature in hepatobiliary disorders: from molecular mechanisms to clinical implications.Medical review (2021) · 2024Review
- Review
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsBiliary disease is associated with a proliferative/fibrogenic ductular reaction (DR). p300 is an epigenetic regulator that acetylates lysine 27 on histone 3 (H3K27ac) and is activated during fibrosis. Long non-coding RNAs (lncRNAs) are aberrantly expressed in cholangiopathies, but little is known about how they recruit epigenetic complexes and regulate DR. We investigated epigenetic complexes, including transcription factors (TFs) and lncRNAs, contributing to p300-mediated transcription during fibrosis.
methodsWe evaluated p300 in vivo using tamoxifen-inducible, cholangiocyte-selective, p300 knockout (KO) coupled with bile duct ligation (BDL) and Mdr KO mice treated with SGC-CBP30. Primary cholangiocytes and liver tissue were analyzed for expression of Acta2-as1 lncRNA by qPCR and RNA in situ hybridization. In vitro, we performed RNA-sequencing in human cholangiocytes with a p300 inhibitor. Cholangiocytes were exposed to lipopolysaccharide (LPS) as an injury model. We confirmed formation of a p300/ELK1 complex by immunoprecipitation (IP). RNA IP was used to examine interactions between ACTA2-AS1 and p300. Chromatin IP assays were used to evaluate p300/ELK1 occupancy and p300-mediated H3K27ac. Organoids were generated from ACTA2-AS1-depleted cholangiocytes.
resultsBDL-induced DR and fibrosis were reduced in Krt19-Cre
conclusionCholangiocyte-selective p300 KO or p300 inhibition attenuate DR/fibrosis in mice. ACTA2-AS1 influences recruitment of p300/ELK1 to specific promoters to drive H3K27ac and epigenetic activation of proliferative/fibrogenic genes. This suggests that cooperation between epigenetic co-activators and lncRNAs facilitates DR/fibrosis in biliary diseases. LAY SUMMARY: We identified a three-part complex containing an RNA molecule, a transcription factor, and an epigenetic enzyme. The complex is active in injured bile duct cells and contributes to activation of genes involved in proliferation and fibrosis.
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