ArticleGut2004
Hepatic fibrogenesis requires sympathetic neurotransmitters.
Article in Gut, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
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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
82 citing papers in PubMed, 218 citations in OpenAlex.
- Catecholamines Activate a Tumour Progression Program in Differentiated Tumour Hepatocytes.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Sympathetic immunomodulation suppresses liver metastasis by maintaining the balance between norepinephrine concentration and the α2a/β2-AR ratio.Cellular & molecular immunology · 2026Article
- Hypothalamic Control of Liver Health and Disease: From Circuits to Pathophysiology and Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Liver-nervous system axis: pathways, dysregulation, and translational perspectives.Journal of neuroinflammation · 2026Review
- Carvedilol decreases hepatic vascular resistance by reducing fibrogenesis and reversing endothelial dysfunction in cirrhotic rats.JHEP reports : innovation in hepatology · 2026Article
- Proliferation of activated hepatic stellate cells requires REST.Molecular medicine (Cambridge, Mass.) · 2026Article
- Liver-nervous system axis in MASLD: mechanistic insights and emerging targeted therapies.eGastroenterology · 2026Review
- Role of central and peripheral serotonin in liver physiology and diseases.Theranostics · 2026Review
- Autoimmunity in MASLD: Focus on autoantibodies, anti-apolipoprotein A1 IgG and G protein-coupled receptors.European journal of clinical investigation · 2025Review
- MicroRNAs in Liver Cirrhosis: Diagnostic and Therapeutic Perspectives-A Comprehensive Review.Journal of personalized medicine · 2025Review
- Roles of Peripheral Nerves in Tumor Initiation and Progression.International journal of molecular sciences · 2025Review
- Effect of Allostatic Load on hepatic steatosis and fatty liver-associated liver fibrosis.BMC gastroenterology · 2025Article
- Role of mitogens in normal and pathological liver regeneration.Hepatology communications · 2025Review
- Dopamine receptors and organ fibrosis.Biochemistry and biophysics reports · 2025Review
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Neuronal injury and hepatotoxicity: astrocytes and stellate cells convergence and their role in tissue repair.Frontiers in neuroscience · 2025Review
- The role of hepatic sinusoidal microenvironment in NASH: pathogenesis, animal models, and therapeutic prospects.Frontiers in pharmacology · 2025Review
- The role of age-related genes in idiopathic pulmonary fibrosis and molecular docking analysis of their drug targets.Frontiers in immunology · 2025Article
- Leveraging adrenergic receptor blockade for enhanced nonalcoholic fatty liver disease treatment via a biomimetic nanoplatform.Journal of nanobiotechnology · 2024Article
- Neuroimmune modulation in liver pathophysiology.Journal of neuroinflammation · 2024Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsHepatic stellate cells (HSC) are activated by liver injury to become proliferative fibrogenic myofibroblasts. This process may be regulated by the sympathetic nervous system (SNS) but the mechanisms involved are unclear.
methodsWe studied cultured HSC and intact mice with liver injury to test the hypothesis that HSC respond to and produce SNS neurotransmitters to promote fibrogenesis.
resultsHSC expressed adrenoceptors, catecholamine biosynthetic enzymes, released norepinephrine (NE), and were growth inhibited by alpha- and beta-adrenoceptor antagonists. HSC from dopamine beta-hydroxylase deficient (Dbh(-/-)) mice, which cannot make NE, grew poorly in culture and were rescued by NE. Inhibitor studies demonstrated that this effect was mediated via G protein coupled adrenoceptors, mitogen activated kinases, and phosphatidylinositol 3-kinase. Injury related fibrogenic responses were inhibited in Dbh(-/-) mice, as evidenced by reduced hepatic accumulation of alpha-smooth muscle actin(+ve) HSC and decreased induction of transforming growth factor beta1 (TGF-beta1) and collagen. Treatment with isoprenaline rescued HSC activation. HSC were also reduced in leptin deficient ob/ob mice which have reduced NE levels and are resistant to hepatic fibrosis. Treating ob/ob mice with NE induced HSC proliferation, upregulated hepatic TGF-beta1 and collagen, and increased liver fibrosis.
conclusionsHSC are hepatic neuroglia that produce and respond to SNS neurotransmitters to promote hepatic fibrosis.
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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.