ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2011
Melatonin inhibits cholangiocyte hyperplasia in cholestatic rats by interaction with MT1 but not MT2 melatonin receptors.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Beneficial effects of melatonin on liver fibrosis: A systematic review of current biological evidence.Journal of cellular physiology · 2022Pooled it
- Banxia Shumi Decoction Alleviates PCPA-Induced Insomnia and Regulates ADAM10 Expression via Melatonin Signaling in Rats.CNS neuroscience & therapeutics · 2026Article
- Morphofunctional State of the Liver Under Conditions of Three-Month Dark Deprivation: The Influence of Circadian Disruptions and Melatonin.International journal of molecular sciences · 2026Article
- Sox9 inhibits Activin A to promote biliary maturation and branching morphogenesis.Nature communications · 2025Article
- Progress in understanding how clock genes regulate aging and associated metabolic processes.Frontiers in physiology · 2025Review
- Article
- Cellular and transcriptional heterogeneity in the intrahepatic biliary epithelium.Gastro hep advances · 2023Article
- Review
- Light-Induced Functional Pinealectomy: Expression of MTBulletin of experimental biology and medicine · 2022Article
- Long-term environmental exposure of darkness induces hyperandrogenism in PCOSFrontiers in cell and developmental biology · 2022Article
- Circadian clock core component Bmal1 dictates cell cycle rhythm of proliferating hepatocytes during liver regeneration.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- The interplay between mast cells, pineal gland, and circadian rhythm: Links between histamine, melatonin, and inflammatory mediators.Journal of pineal research · 2021Review
- Potential Role of Melatonin as an Adjuvant for Atherosclerotic Carotid Arterial Stenosis.Molecules (Basel, Switzerland) · 2021Review
- Melatonin and circadian rhythms in liver diseases: Functional roles and potential therapies.Journal of pineal research · 2020Review
- Review
- Protective role of melatonin in early-stage and end-stage liver cirrhosis.Journal of cellular and molecular medicine · 2019Review
- Possible application of melatonin treatment in human diseases of the biliary tract.American journal of physiology. Gastrointestinal and liver physiology · 2019Review
- Preclinical insights into cholangiopathies: disease modeling and emerging therapeutic targets.Expert opinion on therapeutic targets · 2019Review
- Mel1c Mediated Monochromatic Light-Stimulated IGF-I Synthesis through the Intracellular GInternational journal of molecular sciences · 2019Article
- Ductular Reaction in Liver Diseases: Pathological Mechanisms and Translational Significances.Hepatology (Baltimore, Md.) · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
In bile duct-ligated (BDL) rats, large cholangiocytes proliferate by activation of cAMP-dependent signaling. Melatonin, which is secreted from pineal gland as well as extrapineal tissues, regulates cell mitosis by interacting with melatonin receptors (MT1 and MT2) modulating cAMP and clock genes. In the liver, melatonin suppresses oxidative damage and ameliorates fibrosis. No information exists regarding the role of melatonin in the regulation of biliary hyperplasia. We evaluated the mechanisms of action by which melatonin regulates the growth of cholangiocytes. In normal and BDL rats, we determined the hepatic distribution of MT1, MT2, and the clock genes, CLOCK, BMAL1, CRY1, and PER1. Normal and BDL (immediately after BDL) rats were treated in vivo with melatonin before evaluating 1) serum levels of melatonin, bilirubin, and transaminases; 2) intrahepatic bile duct mass (IBDM) in liver sections; and 3) the expression of MT1 and MT2, clock genes, and PKA phosphorylation. In vitro, large cholangiocytes were stimulated with melatonin in the absence/presence of luzindole (MT1/MT2 antagonist) and 4-phenyl-2-propionamidotetralin (MT2 antagonist) before evaluating cell proliferation, cAMP levels, and PKA phosphorylation. Cholangiocytes express MT1 and MT2, CLOCK, BMAL1, CRY1, and PER1 that were all upregulated following BDL. Administration of melatonin to BDL rats decreased IBDM, serum bilirubin and transaminases levels, the expression of all clock genes, cAMP levels, and PKA phosphorylation in cholangiocytes. In vitro, melatonin decreased the proliferation, cAMP levels, and PKA phosphorylation, decreases that were blocked by luzindole. Melatonin may be important in the management of biliary hyperplasia in human cholangiopathies.
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Registered trials
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.